<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">ometendo</journal-id><journal-title-group><journal-title xml:lang="ru">Ожирение и метаболизм</journal-title><trans-title-group xml:lang="en"><trans-title>Obesity and metabolism</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2071-8713</issn><issn pub-type="epub">2306-5524</issn><publisher><publisher-name>Endocrinology Research Centre</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14341/omet10189</article-id><article-id custom-type="elpub" pub-id-type="custom">ometendo-10189</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Научные исследования</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Original studies</subject></subj-group></article-categories><title-group><article-title>Ассоциация полиморфизма rs2167270 гена лептина (LEP) с интенсивностью боли у больных остеоартритом коленного сустава</article-title><trans-title-group xml:lang="en"><trans-title>Association of the rs2167270 polymorphism of the leptin gene (LEP) with the intensity of pain in patients with osteoarthritis of the knee</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9922-5124</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Крылов</surname><given-names>М. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Krylov</surname><given-names>M. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Крылов Михаил Юрьевич - кандидат медицинских наук; Researcher ID: N-6239-2019; Scopus Author ID: 920397006951088; eLibrary SPIN: 2696-7661.</p><p>115522, Москва, Каширское шоссе, д. 34А</p></bio><bio xml:lang="en"><p>Mikhail Yu. Krylov, MD, PhD; Researcher ID: N-6239-2019; Scopus Author ID: 920397006951088; eLibrary SPIN: 2696-7661.</p><p>Kashirskoe shosse 34A, 115522 Moscow</p></bio><email xlink:type="simple">mekry@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8931-4991</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Алексеева</surname><given-names>Л. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Alekseeva</surname><given-names>L. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Алексеева Людмила Ивановна - доктор медицинских наук, профессор; eLibrary SPIN: 4714-8572</p><p>Москва</p></bio><bio xml:lang="en"><p>Ludmila I. Alekseeva, MD, PhD, Professor; eLibrary SPIN: 4714-8572.</p><p>Moscow</p></bio><email xlink:type="simple">dr.alekseeva@mail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2048-5183</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шарапова</surname><given-names>Е. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Scharapova</surname><given-names>E. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шарапова Евгения Павловна, кандидат медицинских наук; eLibrary SPIN: 9994-0234.</p><p>Москва</p></bio><bio xml:lang="en"><p>Eugenia P. Scharapova MD, PhD, researcher; eLibrary SPIN: 9994-0234.</p><p>Moscow</p></bio><email xlink:type="simple">2116i@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Научно-исследовательский институт ревматологии имени В.А. Насоновой</institution><country>Россия</country></aff><aff xml:lang="en"><institution>V.A. Nasonova Research Institute of Rheumatology</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>24</day><month>07</month><year>2021</year></pub-date><volume>18</volume><issue>2</issue><fpage>210</fpage><lpage>217</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Крылов М.Ю., Алексеева Л.И., Шарапова Е.П., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Крылов М.Ю., Алексеева Л.И., Шарапова Е.П.</copyright-holder><copyright-holder xml:lang="en">Krylov M.Y., Alekseeva L.I., Scharapova E.P.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.omet-endojournals.ru/jour/article/view/10189">https://www.omet-endojournals.ru/jour/article/view/10189</self-uri><abstract><sec><title>Обоснование</title><p>Обоснование. Остеоартрит (ОА) — значимая социальная проблема, так как является самым частым заболеванием суставов. ОА является многофакторным заболеванием, при котором большое внимание уделяется роли наследственных факторов. В последнее время ряд исследований продемонстрировал вклад ряда генов в субъективную оценку боли при ОА, которая является главным симптомом этого заболевания. Была показана связь генов P2X7, TRPV1 и TACR1 и некоторых других с чувствительностью к боли. Одним из факторов риска возникновения боли, среди многих других, является повышенный вес. Абдоминальная жировая ткань является источником высвобождения провоспалительных адипокинов, вызывающих системное воспаление, связанное с повреждением многих тканей, включая субхондральную кость, синовиальную оболочку. Лептин является эндогенным гормоном из семейства адипокинов, кодируемым геном ожирения лептином (LEP), который синтезируется главным образом в адипоцитах. Роль гена LEP в субъективной оценке боли при ОА в отечественных исследованиях не изучалась.</p></sec><sec><title>Цель</title><p>Цель. Изучить возможную связь полиморфизма rs2167270 (A19G) гена LEP с интенсивностью боли у больных ОА коленного сустава.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Исследование проведено среди женщин с диагнозом ОА. Используя шкалу ВАШ (Визуальная аналоговая шкала) для оценки субъективной боли самим пациентом, были изучены пациентки со слабой болью в коленном ­суставе — группа 1 (индекс ВАШ ≤40 мм) и пациентки с умеренной или выраженной болью — группа 2 (индекс ВАШ &gt;40 мм). Генетические варианты A19G полиморфизма гена лептина были изучены с помощью полимеразной цепной реакции с последующим анализом длин рестриктных фрагментов (ПЦР-ПДРФ метод).</p></sec><sec><title>Результаты</title><p>Результаты. В группе пациентов с умеренной или выраженной интенсивностью боли (группа 2, n=61) по сравнению с группой 1 (n=36) показана статистически значимая связь с высоким индексом массы тела (р=0,006). В этой группе пациентов выявлена повышенная частота носителей 19GG генотипа (р=0,051) по сравнению с группой 1. Носители 19GG генотипа статистически значимо имели более высокий показатель ВАШ в коленном суставе и ранний возраст дебюта ОА по сравнению с носителями генотипа 19AA (р=0,035 и р=0,015 соответственно).</p></sec><sec><title>Заключение</title><p>Заключение. Полученные данные открывают новые возможности прогнозирования болевого симптома у больных ОА коленного сустава путем генетического тестирования A19G полиморфных вариантов гена LEP.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background: Osteoarthritis (OA) is a significant social problem as it is the most common disease of the joints. OA is a multifactorial disease in which great attention is paid to hereditary factors. Recently, a number of studies have demonstrated the contribution of a number of genes to the subjective assessment of pain in OA, which is the main symptom of this disease. The association of P2X7, TRPV1 and TACR1 genes and some others with pain sensitivity has been shown. One of the risk factors of pain among many others, is the increased weight. Abdominal adipose tissue is a source of release of pro-inflammatory adipokines that cause systemic inflammation associated with damage to many tissues, including subchondral bone, synovial membrane. Leptin is an endogenous hormone from the adipokine family encoded by the obesity gene leptin (LEP) and which is synthesized primarily in adipocytes.</p></sec><sec><title>Aims</title><p>Aims: To investigate the possible association of rs2167270 (A19G) polymorphism of the LEP gene with pain intensity in ­patients with knee OA.</p></sec><sec><title>Materials and methods</title><p>Materials and methods: The study was conducted among women diagnosed with OA. Using the VAS scale (Visual analog scale), patients with mild knee pain — group 1 (VAS ≤ 40 mm) and patients with moderate or severe pain — group 2 (VAS&gt;40 mm) were selected for pain assessment. Genetic variants of A19G leptin gene polymorphism were studied by polymerase chain reaction followed by restriction fragment length analysis (PCR-RFLP) method.</p></sec><sec><title>Results</title><p>Results: In the group of patients with moderate or severe pain intensity (group 2, n=61), a statistically significant association was shown with a higher body mass index (p=0.006) and an increased frequency of carriers of the 19GG genotype (p=0,051) compared to group 1 (n=36). Carriers of the 19GG genotype statistically significantly had a higher rate of knee pain and an early age of OA debut compared to carriers of the 19AA genotype (p=0,035 and p=0,015, respectively).</p></sec><sec><title>Conclusions</title><p>Conclusions: The findings open up new possibilities for predicting pain symptoms in patients with knee OA by genetic testing of A19G polymorphic variants of the leptin gene.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>остеоартрит коленного сустава</kwd><kwd>боль по ВАШ</kwd><kwd>ожирение</kwd><kwd>индекс массы тела</kwd><kwd>полиморфизм rs2167270 гена LEP</kwd></kwd-group><kwd-group xml:lang="en"><kwd>knee osteoarthritis</kwd><kwd>pain</kwd><kwd>obesity</kwd><kwd>BMI</kwd><kwd>polymorphism rs2167270 LEP gene</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена на базе НИИР им. В.А. Насоновой с привлечением средств учреждения. Авторы выражают слова благодарности врачам отдела метаболических заболеваний костей и суставов Института ревматологии им. В.А. Насоновой за помощь в отборе пациентов для настоящего исследования</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Ревматология. Клинические рекомендации / Под ред. Е.Л. Насонова— М.; 2010. — 326 с.</mixed-citation><mixed-citation xml:lang="en">Rheumatology. Clinical Recommendations. Ed. by Nasonov EL. Moscow; 2010. 326 p. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Фоломеева О.М., Галушко Е.А., Эрдес Ш.Ф. Распространенность ревматических заболеваний в популяциях взрослого населения России и США // Научно-практическая ревматология. — 2008. — Т. 12. — №4. — С. 4-13. doi: https://doi.org/10.14412/1995-4484-2008-529</mixed-citation><mixed-citation xml:lang="en">Folomeeva OM, Galushko EA, Erdes SF. Prevalence of rheumatic diseases in adult populations of Russian Federation and USA. Rheumatol Sci Pract. 2008;12(4):4-14. (In Russ.). doi: https://doi.org/10.14412/1995-4484-2008-529</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol. 2007;213(3):626-634. doi: https://doi.org/10.1002/jcp.21258</mixed-citation><mixed-citation xml:lang="en">Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol. 2007;213(3):626-634. doi: https://doi.org/10.1002/jcp.21258</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Стребкова Е.А., Алексеева Л.И. Остеоартроз и ожирение // Научно-практическая ревматология. — 2015. — Т. 53. — №5. — С. 542-552 [Strebkova EA, Alekseeva LI. Osteoarthritis and obesity. Rheumatol Sci Pract. 2015;53(5):542-552. (In Russ.)]. doi: https://doi.org/10.14412/1995-4484-2015-542-552</mixed-citation><mixed-citation xml:lang="en">Стребкова Е.А., Алексеева Л.И. Остеоартроз и ожирение // Научно-практическая ревматология. — 2015. — Т. 53. — №5. — С. 542-552 [Strebkova EA, Alekseeva LI. Osteoarthritis and obesity. Rheumatol Sci Pract. 2015;53(5):542-552. (In Russ.)]. doi: https://doi.org/10.14412/1995-4484-2015-542-552</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Spector TD, MacGregor AJ. Risk factors for osteoarthritis: genetics. Osteoarthr Cartil. 2004;12:39-44. doi: https://doi.org/10.1016/j.joca.2003.09.005</mixed-citation><mixed-citation xml:lang="en">Spector TD, MacGregor AJ. Risk factors for osteoarthritis: genetics. Osteoarthr Cartil. 2004;12:39-44. doi: https://doi.org/10.1016/j.joca.2003.09.005</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Valdes AM, Spector TD. Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol. 2011;7(1):23-32. doi: https://doi.org/10.1038/nrrheum.2010.191</mixed-citation><mixed-citation xml:lang="en">Valdes AM, Spector TD. Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol. 2011;7(1):23-32. doi: https://doi.org/10.1038/nrrheum.2010.191</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004;15(11):2792-2800. doi: https://doi.org/10.1097/01.ASN.0000141966.69934.21</mixed-citation><mixed-citation xml:lang="en">Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004;15(11):2792-2800. doi: https://doi.org/10.1097/01.ASN.0000141966.69934.21</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Berenbaum F, Griffin TM, Liu-Bryan R. Review: Metabolic Regulation of Inflammation in Osteoarthritis. Arthritis Rheumatol. 2017;69(1):9-21. doi: https://doi.org/10.1002/art.39842</mixed-citation><mixed-citation xml:lang="en">Berenbaum F, Griffin TM, Liu-Bryan R. Review: Metabolic Regulation of Inflammation in Osteoarthritis. Arthritis Rheumatol. 2017;69(1):9-21. doi: https://doi.org/10.1002/art.39842</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Ioan-Facsinay A, Kloppenburg M. An emerging player in knee osteoarthritis: the infrapatellar fat pad. Arthritis Res Ther. 2013;15(6):225. doi: https://doi.org/10.1186/ar4422</mixed-citation><mixed-citation xml:lang="en">Ioan-Facsinay A, Kloppenburg M. An emerging player in knee osteoarthritis: the infrapatellar fat pad. Arthritis Res Ther. 2013;15(6):225. doi: https://doi.org/10.1186/ar4422</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Pitsavos C, Tampourlou M, Panagiotakos DB, et al. Association Between Low-Grade Systemic Inflammation and Type 2 Diabetes Mellitus Among Men and Women from the ATTICA Study. Rev Diabet Stud. 2007;4(2):98-104. doi: https://doi.org/10.1900/RDS.2007.4.98</mixed-citation><mixed-citation xml:lang="en">Pitsavos C, Tampourlou M, Panagiotakos DB, et al. Association Between Low-Grade Systemic Inflammation and Type 2 Diabetes Mellitus Among Men and Women from the ATTICA Study. Rev Diabet Stud. 2007;4(2):98-104. doi: https://doi.org/10.1900/RDS.2007.4.98</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Woods AJ, Stock MJ. Leptin activation in hypothalamus. Nature. 1996;381(6585):745-745. doi: https://doi.org/10.1038/381745a0</mixed-citation><mixed-citation xml:lang="en">Woods AJ, Stock MJ. Leptin activation in hypothalamus. Nature. 1996;381(6585):745-745. doi: https://doi.org/10.1038/381745a0</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Dumond H, Presle N, Terlain B, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118-3129. doi: https://doi.org/10.1002/art.11303</mixed-citation><mixed-citation xml:lang="en">Dumond H, Presle N, Terlain B, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118-3129. doi: https://doi.org/10.1002/art.11303</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Neumann E, Junker S, Schett G, et al. Adipokines in bone disease. Nat Rev Rheumatol. 2016;12(5):296-302. doi: https://doi.org/10.1038/nrrheum.2016.49</mixed-citation><mixed-citation xml:lang="en">Neumann E, Junker S, Schett G, et al. Adipokines in bone disease. Nat Rev Rheumatol. 2016;12(5):296-302. doi: https://doi.org/10.1038/nrrheum.2016.49</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Gandhi R, Takahashi M, Smith H, et al. The synovial fluid adiponectin-leptin ratio predicts pain with knee osteoarthritis. Clin Rheumatol. 2010;29(11):1223-1228. doi: https://doi.org/10.1007/s10067-010-1429-z</mixed-citation><mixed-citation xml:lang="en">Gandhi R, Takahashi M, Smith H, et al. The synovial fluid adiponectin-leptin ratio predicts pain with knee osteoarthritis. Clin Rheumatol. 2010;29(11):1223-1228. doi: https://doi.org/10.1007/s10067-010-1429-z</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Gandhi R, Kapoor M, Mahomed NN, Perruccio AV. A comparison of obesity related adipokine concentrations in knee and shoulder osteoarthritis patients. Obes Res Clin Pract. 2015;9(4):420-423. doi: https://doi.org/10.1016/j.orcp.2015.02.003</mixed-citation><mixed-citation xml:lang="en">Gandhi R, Kapoor M, Mahomed NN, Perruccio AV. A comparison of obesity related adipokine concentrations in knee and shoulder osteoarthritis patients. Obes Res Clin Pract. 2015;9(4):420-423. doi: https://doi.org/10.1016/j.orcp.2015.02.003</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Gandhi R, Sharma A, Kapoor M, et al. Racial Differences in Serum Adipokine and Insulin Levels in a Matched Osteoarthritis Sample: A Pilot Study. J Obes. 2016;2016:1-5. doi: https://doi.org/10.1155/2016/8746268</mixed-citation><mixed-citation xml:lang="en">Gandhi R, Sharma A, Kapoor M, et al. Racial Differences in Serum Adipokine and Insulin Levels in a Matched Osteoarthritis Sample: A Pilot Study. J Obes. 2016;2016:1-5. doi: https://doi.org/10.1155/2016/8746268</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Videman T, Gibbons LE, Kaprio J, Battie MC. Challenging the cumulative injury model: positive effects of greater body mass on disc degeneration. Spine J. 2010;10(1):26-31.doi: https://doi.org/10.1016/j.spinee.2009.10.005</mixed-citation><mixed-citation xml:lang="en">Videman T, Gibbons LE, Kaprio J, Battie MC. Challenging the cumulative injury model: positive effects of greater body mass on disc degeneration. Spine J. 2010;10(1):26-31.doi: https://doi.org/10.1016/j.spinee.2009.10.005</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Fasshauer M, Bluher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015;36(7):461-470. doi: https://doi.org/10.1016/j.tips.2015.04.014</mixed-citation><mixed-citation xml:lang="en">Fasshauer M, Bluher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015;36(7):461-470. doi: https://doi.org/10.1016/j.tips.2015.04.014</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Isse N., Ogawa Y, Tamura N, et al. Structural organization and chromosomal assignment of the human obese gene. J Biol Chem. 1995;270(46):27728-27733. doi: https://doi.org/10.1074/jbc.270.46.27728</mixed-citation><mixed-citation xml:lang="en">Isse N., Ogawa Y, Tamura N, et al. Structural organization and chromosomal assignment of the human obese gene. J Biol Chem. 1995;270(46):27728-27733. doi: https://doi.org/10.1074/jbc.270.46.27728</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Eitner A, Hofmann GO, Schaible HG. Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models. Front Mol Neurosci. 2017;10:349. doi: https://doi.org/10.3389/fnmol.2017.00349</mixed-citation><mixed-citation xml:lang="en">Eitner A, Hofmann GO, Schaible HG. Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models. Front Mol Neurosci. 2017;10:349. doi: https://doi.org/10.3389/fnmol.2017.00349</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Marks R. Obesity Profiles with Knee Osteoarthritis: Correlation with Pain, Disability, Disease Progression. Obesity. 2007;15(7):1867-1874. doi: https://doi.org/10.1038/oby.2007.221</mixed-citation><mixed-citation xml:lang="en">Marks R. Obesity Profiles with Knee Osteoarthritis: Correlation with Pain, Disability, Disease Progression. Obesity. 2007;15(7):1867-1874. doi: https://doi.org/10.1038/oby.2007.221</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of knee. Arthritis Rheum.1986;29(8):1039-1049. doi: https://doi.org/10.1002/art.1780290816</mixed-citation><mixed-citation xml:lang="en">Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of knee. Arthritis Rheum.1986;29(8):1039-1049. doi: https://doi.org/10.1002/art.1780290816</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Крылов М.Ю., Беневоленская Л.И., Мякоткин В.А. Полиморфизм A19G гена лептина и полиморфизмы Gln223Arg и Lys109Arg гена рецептора лептина при постменопаузальном остеопорозе // Научно-практическая ревматология. — 2010. — Т. 15. — №5. — С. 27-30.. doi: https://doi.org/10.14412/1995-4484-2010-727</mixed-citation><mixed-citation xml:lang="en">Krylov MY, Benevolenskaya LI, Myakotkin VA. Leptin A19G polymorphism and leptin receptor Gln223Arg and Lys109Arg polymorphismsin postmenopausal osteoporosis. Rheumatol Sci Pract. 2010;15(5):27-30 (In Russ.). doi: https://doi.org/10.14412/1995-4484-2010-727</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Simopoulou T, Malizos KN, Iliopoulos D, et al. Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarthritis Cartilage. 2007;15(8):872-883. doi: https://doi.org/10.1016/j.joca.2007.01.018</mixed-citation><mixed-citation xml:lang="en">Simopoulou T, Malizos KN, Iliopoulos D, et al. Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarthritis Cartilage. 2007;15(8):872-883. doi: https://doi.org/10.1016/j.joca.2007.01.018</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Plotnikoff R, Karunamuni N, Lytvyak E, et al. Osteoarthritis prevalence and modifiable factors: a population study. BMC Public Health. 2015;15:1195. doi: https://doi.org/10.1186/s12889-015-2529-0</mixed-citation><mixed-citation xml:lang="en">Plotnikoff R, Karunamuni N, Lytvyak E, et al. Osteoarthritis prevalence and modifiable factors: a population study. BMC Public Health. 2015;15:1195. doi: https://doi.org/10.1186/s12889-015-2529-0</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013;105:185-199. doi: https://doi.org/10.1093/bmb/Ids038</mixed-citation><mixed-citation xml:lang="en">Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013;105:185-199. doi: https://doi.org/10.1093/bmb/Ids038</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2010;18(1):24-33. doi: https://doi.org/10.1016/j.joca.2009.08.010</mixed-citation><mixed-citation xml:lang="en">Blagojevic M, Jinks C, Jeffery A, Jordan KP. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2010;18(1):24-33. doi: https://doi.org/10.1016/j.joca.2009.08.010</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Grotle M, Hagen KB, Natvig B, et al. Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord. 2008;9:132. doi: https://doi.org/10.1186/1471-2474-9-132</mixed-citation><mixed-citation xml:lang="en">Grotle M, Hagen KB, Natvig B, et al. Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord. 2008;9:132. doi: https://doi.org/10.1186/1471-2474-9-132</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Murphy L, Schwartz TA, Helmick CG, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Care Res. 2008;59(9):1207-1213. doi: https://doi.org/10.1002/art.24021</mixed-citation><mixed-citation xml:lang="en">Murphy L, Schwartz TA, Helmick CG, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Care Res. 2008;59(9):1207-1213. doi: https://doi.org/10.1002/art.24021</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Felson DT, Zhang Y, Anthony JM, et al. Weight loss reduces the risk for symptomatic knee osteoarthritis in women The Framingham Study. Ann Intern Med. 1992;116(7):535-539. doi: https://doi.org/10.7326/0003-4819-116-7-535</mixed-citation><mixed-citation xml:lang="en">Felson DT, Zhang Y, Anthony JM, et al. Weight loss reduces the risk for symptomatic knee osteoarthritis in women The Framingham Study. Ann Intern Med. 1992;116(7):535-539. doi: https://doi.org/10.7326/0003-4819-116-7-535</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Ackerman IN, Osborne RH. Obesity and increased burden of hip and knee joint disease in Australia: Results from a national survey. BMC Musculoskelet Disord. 2012;13(1):254. doi: https://doi.org/10.1186/1471-2474-13-254</mixed-citation><mixed-citation xml:lang="en">Ackerman IN, Osborne RH. Obesity and increased burden of hip and knee joint disease in Australia: Results from a national survey. BMC Musculoskelet Disord. 2012;13(1):254. doi: https://doi.org/10.1186/1471-2474-13-254</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Hager J, Clément K, Francke S, et al. A polymorphism in the 5’ untranslated region of the human ob gene is associated with low leptin levels. Int J Obes Relat Matab Disord. 1998;22(3):200-205. doi: https://doi.org/10.1038/sj.ijo.0800567</mixed-citation><mixed-citation xml:lang="en">Hager J, Clément K, Francke S, et al. A polymorphism in the 5’ untranslated region of the human ob gene is associated with low leptin levels. Int J Obes Relat Matab Disord. 1998;22(3):200-205. doi: https://doi.org/10.1038/sj.ijo.0800567</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Lucantoni R, Ponti E, Berselli ME, et al. The A19G Polymorphism in the 5’ Untranslated Region of the Human Obese GeneDoes Not Affect Leptin Levels in Severely Obese Patients. J Clin Endocrinol Metab. 2000;85(10):3589-3591. doi: https://doi.org/10.1210/jcem.85.10.6860</mixed-citation><mixed-citation xml:lang="en">Lucantoni R, Ponti E, Berselli ME, et al. The A19G Polymorphism in the 5’ Untranslated Region of the Human Obese GeneDoes Not Affect Leptin Levels in Severely Obese Patients. J Clin Endocrinol Metab. 2000;85(10):3589-3591. doi: https://doi.org/10.1210/jcem.85.10.6860</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Karvonen MK, Pesonen U, Heinonen P, et al. Identification of new sequence variant in the leptin gene. J Clin Endocrinol Metab. 1998;83(9):3239-3242. doi: https://doi.org/10.1210/jcem.83.9.5135</mixed-citation><mixed-citation xml:lang="en">Karvonen MK, Pesonen U, Heinonen P, et al. Identification of new sequence variant in the leptin gene. J Clin Endocrinol Metab. 1998;83(9):3239-3242. doi: https://doi.org/10.1210/jcem.83.9.5135</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">van Meurs JB, Uitterlinden AG, Stolk L, et al. A functional polymorphism in the catechol-O-methyltransferase gene is associated with osteoarthritis-related pain. ArthritisRheumatol. 2009;60(2):628-629. doi: https://doi.org/10.1002/art.24175</mixed-citation><mixed-citation xml:lang="en">van Meurs JB, Uitterlinden AG, Stolk L, et al. A functional polymorphism in the catechol-O-methyltransferase gene is associated with osteoarthritis-related pain. ArthritisRheumatol. 2009;60(2):628-629. doi: https://doi.org/10.1002/art.24175</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Neogi T, Soni A, Doherty SA, et al. Contribution of the COMT Val158Met variant to symptomatic knee osteoarthritis. Ann Rheum Dis. 2014;73(1):315-317. doi: https://doi.org/10.1136/annrheumdis-2013-203836</mixed-citation><mixed-citation xml:lang="en">Neogi T, Soni A, Doherty SA, et al. Contribution of the COMT Val158Met variant to symptomatic knee osteoarthritis. Ann Rheum Dis. 2014;73(1):315-317. doi: https://doi.org/10.1136/annrheumdis-2013-203836</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Valdes AM, De Wilde G, Doherty SA, et al. The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis. Ann Rheum Dis. 2011;70(9):1556-1561. doi: https://doi.org/10.1136/ard.2010.148122</mixed-citation><mixed-citation xml:lang="en">Valdes AM, De Wilde G, Doherty SA, et al. The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis. Ann Rheum Dis. 2011;70(9):1556-1561. doi: https://doi.org/10.1136/ard.2010.148122</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Olesen AE, Nielsen LM, Feddersen S, et al. Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis. Pain Pract. 2018;18(5):587-596. doi: https://doi.org/10.1111/papr.12648</mixed-citation><mixed-citation xml:lang="en">Olesen AE, Nielsen LM, Feddersen S, et al. Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis. Pain Pract. 2018;18(5):587-596. doi: https://doi.org/10.1111/papr.12648</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Malfait AM, Seymour AB, Gao F, et al. A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype. Ann Rheum Dis. 2012;71(6):1042-1048. doi: https://doi.org/10.1136/annrheumdis-2011-200300</mixed-citation><mixed-citation xml:lang="en">Malfait AM, Seymour AB, Gao F, et al. A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype. Ann Rheum Dis. 2012;71(6):1042-1048. doi: https://doi.org/10.1136/annrheumdis-2011-200300</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Reimann F., Cox J.J., Belfer I, et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci USA. 2010;107(11):5148-5153. doi: https://doi.org/10.1073/pnas.0913181107</mixed-citation><mixed-citation xml:lang="en">Reimann F., Cox J.J., Belfer I, et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci USA. 2010;107(11):5148-5153. doi: https://doi.org/10.1073/pnas.0913181107</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Tsepilov YA, Freidin MB, Shadrina AS, et al. Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions. Commun Biol. 2020;3(1):329. doi: https://doi.org/10.1038/s42003-020-1051-9</mixed-citation><mixed-citation xml:lang="en">Tsepilov YA, Freidin MB, Shadrina AS, et al. Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions. Commun Biol. 2020;3(1):329. doi: https://doi.org/10.1038/s42003-020-1051-9</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
