ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet9680ometendo-9680Research ArticleОригинальные исследованияOriginal paperВлияние полиморфизма гена MC4R на антропометрические параметры у подростков с избыточной массой тела и ожирениемEffect of MC4R gene polymorphism on food intake in adolescents with overweight and obesityhttps://orcid.org/0000-0002-0177-234XИевлеваКсения ДмитриевнаIevlevaKseniya D.

аспирант, отдел персонализированной и профилактической медицины, лаборатория персонализированной медицины

MD, postgraduade student

asiy91@mail.ruБаироваТатьяна АнаньевнаBairovaTatyana A.

д.м.н., заместитель директора по научной работе

MD, PhD

tbairova38@mail.ruШенеманЕкатерина АлексеевнаShenemanEkaterina A.

аспирант

MD, postgraduade student

sheneman@bk.ruБальжиеваВарвара ВладимировнаBalzhievaVarvara V.

аспирант

MD, postgraduade student

varvara.balzhieva@yandex.ruАюроваЖанна ГармаевнаAyurovaZhanna G.

аспирант

MD, postgraduade student

zhanna.irk@mail.ruhttps://orcid.org/0000-0002-0117-2563РычковаЛюбовь ВладимировнаRychkovaLubov V.

д.м.н., проф., директор

MD, PhD, professor

iphr@sbamsr.irk.ruhttps://orcid.org/0000-0003-3354-2992КолесниковаЛюбовь ИльиничнаKolesnikovaLubov I.

академик РАН, д.м.н., проф., научный руководитель

MD, PhD, professor

iphr@sbamsr.irk.ru<p>ФГБНУ &laquo;Научный центр проблем здоровья семьи и репродукции человека&raquo;</p>Россия<p>Scientific Сentre of Family Health and Human Reproduction Problems</p>Russian Federation2019160920191622228Copyright &#x00A9; Иевлева К.Д., Баирова Т.А., Шенеман Е.А., Бальжиева В.В., Аюрова Ж.Г., Рычкова Л.В., Колесникова Л.И., 20192019Иевлева К.Д., Баирова Т.А., Шенеман Е.А., Бальжиева В.В., Аюрова Ж.Г., Рычкова Л.В., Колесникова Л.И.Ievleva K.D., Bairova T.A., Sheneman E.A., Balzhieva V.V., Ayurova Z.G., Rychkova L.V., Kolesnikova L.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/9680Обоснование

Обоснование. Ген рецептора меланокортина 4 (MC4R) кодирует информацию об одноименном рецепторе, экспрессируемом в гипоталамусе и участвующем в регуляции массы тела и роста. Данные о вкладе полиморфизма MC4R rs17782313 противоречивы.

Цель исследования – изучить влияние носительства полиморфизма MC4R rs17782313 на антропометрические параметры у подростков разных этнических групп: европеоидов и монголоидов, проживающих на территории Сибири.

Методы

Методы. В исследование включены 179 подростков европеоидной расы (на примере русских, средний возраст 15,07±1,25 лет) и 182 подростка монголоидной расы (на примере бурят, средний возраст 14,71±1,28 лет). В группы с избыточной массой тела и ожирением (SDS ИМТ>1) вошли 89 и 92 подростка, в контрольные группы (SDS ИМТ от –1 до +1) – 90 и 90 подростков русской и бурятской национальностей соответственно. Антропометрическое обследование включало измерение роста, массы тела с расчетом ИМТ (индекс массы тела) и SDS ИМТ (коэффициент стандартного отклонения ИМТ), ОТ (объем талии), ОБ (объем бедер). Генотипирование ДНК-образов, выделенных из цельной венозной крови, осуществлялось методом ПЦР в реальном времени. Статистический анализ результатов исследования проводился с использованием программного обеспечения STATISTICA 8.0.

Результаты

Результаты. Расчет отношения шансов показал отсутствие ассоциации рискового С-аллеля полиморфизма rs17782313 с избыточной массой тела и ожирением у подростков в выборке русских (22,5% против 17,9%; OR=1,34 (р>0,05) и в выборке бурят (29,8% против 24,1%, OR=1,43 (р>0,05). Выявлено, что у подростков-носителей С-аллеля бурятской национальности наблюдается более высокий рост в обеих группах (контроль: 162,19 см против 157,26 см; р=0,019; основная: 165,24 см против 164,91 см; р=0,041), а также увеличение веса в контрольной группе (52,29 кг против 48,05 кг, р=0,028).

Заключение

Заключение. Таким образом, выявлена взаимосвязь полиморфизма MC4R rs17782313 с ростом и весом у подростков бурятской национальности.

BACKGROUND

BACKGROUND: The melanocortin 4 receptor gene (MC4R) codes the receptor expressed in the hypothalamus and involved in the regulation of body mass and height. Data on the association of polymorphism MC4R rs17782313 with anthropometric parameters are contradictory.

AIMS

AIMS: to study the influence of the carrier of polymorphism MC4R rs17782313 on the anthropometric parameters in adolescents of different ethnic groups: caucasians and mongoloids living in the Siberia.

MATERIALS AND METHODS

MATERIALS AND METHODS: The study included 179 caucasian adolescents (by the example of russians, average age is 15.07 ± 1.25 years) and 182 mongoloid adolescents (by the example of the buryats, the average age is 14.71 ± 1.28 years), 89 and 92 adolescents were included in groups with overweight and obesity (standard deviation (SDS) BMI> 1), in the control groups (SDS BMI from -1 to + 1) also 90 and 90 adolescents were included in the control groups (SDS BMI from -1 to + 1) (russian and buryat, respectively). Anthropometric measurements included height, weight with the calculation of BMI and SDS BMI, WC (waist circumference), HC (hip circumference ). Genotyping was performed by real-time PCR. Statistical analysis of the results of the study was carried out using the software «STATISTICA 8.0».

RESULTS

RESULTS: We showed no association of the risky C-allele of polymorphism rs17782313 with overweight and obesity in russian adolescents (22.5% vs 17.9% OR = 1.34 (p> 0.05)) and in the buryat (29.8% vs 24.1%, OR = 1.43 (p> 0.05)). It was revealed that adolescent carriers of the C-allele in buryat showed higher growth in both groups (control: 162.19 cm vs 157.26 cm (p = 0.019)), the main group: 165.24 cm vs 164.91 cm (p = 0.041)), as well as weight gain in the control group (52.29 kg vs 48.05 kg (p = 0.028)).

CONCLUSIONS

CONCLUSIONS: Thus, the study revealed the relationship of MC4R rs17782313 polymorphism with height and weight in adolescents of buryat ethnic group.

ожирениеизбыточная масса теларостподросткиMC4RевропеоидымонголоидыobesityoverweightadolescentsMC4Rfood intakeReferencesДедов И.И., Мельниченко Г.А., Бутрова С.А. Ожирение у подростков в России // Терапевтический архив. – 2007. – №10. – С.28-32. [Dedov II, Mel'nichenko GA, Butrova SA. Ozhirenie u podrostkov v Rossii. Terapevticheskiĭ arkhiv. 2007;(10):28–32. (In Russ.)]Дедов И.И., Мельниченко Г.А., Бутрова С.А. Ожирение у подростков в России // Терапевтический архив. – 2007. – №10. – С.28-32. [Dedov II, Mel'nichenko GA, Butrova SA. Ozhirenie u podrostkov v Rossii. Terapevticheskiĭ arkhiv. 2007;(10):28–32. (In Russ.)]Бальжиева В.В., Баирова Т.А., Рычкова Л.В., и др. Этногенетические аспекты ожирения у детей и подростков // Вопросы детской диетологии. – 2017. – Т.15. – №5. – С.29-34. [Balzhieva VV, Bairova TA, Rychkova LV, et al. Ethnogenetic aspects of obesity in children and adolescents. Vopr Det Dietol. 2017;15(5):29-34. (In Russ.)] doi: 10.20953/1727-5784-2017-5-29-34Бальжиева В.В., Баирова Т.А., Рычкова Л.В., и др. Этногенетические аспекты ожирения у детей и подростков // Вопросы детской диетологии. – 2017. – Т.15. – №5. – С.29-34. [Balzhieva VV, Bairova TA, Rychkova LV, et al. Ethnogenetic aspects of obesity in children and adolescents. Vopr Det Dietol. 2017;15(5):29-34. (In Russ.)] doi: 10.20953/1727-5784-2017-5-29-34Liu G, Zhu H, Dong Y, et al. Influence of common variants in FTO and near INSIG2 and MC4R on growth curves for adiposity in African– and European–American youth. Eur J Epidemiol. 2011;26(6):463-473. doi: 10.1007/s10654-011-9583-4Liu G, Zhu H, Dong Y, et al. Influence of common variants in FTO and near INSIG2 and MC4R on growth curves for adiposity in African– and European–American youth. Eur J Epidemiol. 2011;26(6):463-473. doi: 10.1007/s10654-011-9583-4Баирова Т.А., Шенеман Е.А., Рычкова Л.В., Иевлева К.Д. Ген FTO и его роль в развитии ожирения и избыточной массы тела у детей Т.А. // Педиатрия. Журнал им. Г.Н. Сперанского. – 2017. – Т.96. – №4. – С.186-193. [Bairova TA, Sheneman EA, Rychkova L V, Ievleva KD. FTO gene and its role in development of obesity and excessive body weight in children. Pediatr J named after GN Speransky. 2017;96(4):186-193 (In Russ.)] doi: 10.24110/0031-403X-2017-96-4-186-193Баирова Т.А., Шенеман Е.А., Рычкова Л.В., Иевлева К.Д. Ген FTO и его роль в развитии ожирения и избыточной массы тела у детей Т.А. // Педиатрия. Журнал им. Г.Н. Сперанского. – 2017. – Т.96. – №4. – С.186-193. [Bairova TA, Sheneman EA, Rychkova L V, Ievleva KD. FTO gene and its role in development of obesity and excessive body weight in children. Pediatr J named after GN Speransky. 2017;96(4):186-193 (In Russ.)] doi: 10.24110/0031-403X-2017-96-4-186-193Gahagan S. Overweight and obesity. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier; 2016:chap 47.Gahagan S. Overweight and obesity. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier; 2016:chap 47.Hinney A, Volckmar A-L, Knoll N. Melanocortin-4 Receptor in Energy Homeostasis and Obesity Pathogenesis. Prog Mol Biol Transl Sci. 2013;114:147-191. doi: 10.1016/B978-0-12-386933-3.00005-4Hinney A, Volckmar A-L, Knoll N. Melanocortin-4 Receptor in Energy Homeostasis and Obesity Pathogenesis. Prog Mol Biol Transl Sci. 2013;114:147-191. doi: 10.1016/B978-0-12-386933-3.00005-4Cheung CYY, Tso AWK, Cheung BMY, et al. Obesity Susceptibility Genetic Variants Identified from Recent Genome-Wide Association Studies: Implications in a Chinese Population. J Clin Endocrinol Metab. 2010;95(3):1395-1403. doi: 10.1210/jc.2009-1465Cheung CYY, Tso AWK, Cheung BMY, et al. Obesity Susceptibility Genetic Variants Identified from Recent Genome-Wide Association Studies: Implications in a Chinese Population. J Clin Endocrinol Metab. 2010;95(3):1395-1403. doi: 10.1210/jc.2009-1465Xi B, Chandak GR, Shen Y, et al. Association between Common Polymorphism near the MC4R Gene and Obesity Risk: A Systematic Review and Meta-Analysis. PLoS One. 2012;7(9):e45731. doi: 10.1371/journal.pone.0045731Xi B, Chandak GR, Shen Y, et al. Association between Common Polymorphism near the MC4R Gene and Obesity Risk: A Systematic Review and Meta-Analysis. PLoS One. 2012;7(9):e45731. doi: 10.1371/journal.pone.0045731Wu L, Xi B, Zhang M, et al. Associations of Six Single Nucleotide Polymorphisms in Obesity-Related Genes With BMI and Risk of Obesity in Chinese Children. Diabetes. 2010;59(12):3085-3089. doi: 10.2337/db10-0273Wu L, Xi B, Zhang M, et al. Associations of Six Single Nucleotide Polymorphisms in Obesity-Related Genes With BMI and Risk of Obesity in Chinese Children. Diabetes. 2010;59(12):3085-3089. doi: 10.2337/db10-0273Ievleva K, Bairova T, Sheneman E, Kolesnikova L. Carriers of mc4r rs17782313 in female adolescents with overweight and obesity. Acta Paediatr. 2017;106(S470):27-28. doi: 10.1111/apa.14094Ievleva K, Bairova T, Sheneman E, Kolesnikova L. Carriers of mc4r rs17782313 in female adolescents with overweight and obesity. Acta Paediatr. 2017;106(S470):27-28. doi: 10.1111/apa.14094Srivastava A, Mittal B, Prakash J, et al. Evaluation of MC4R [rs17782313, rs17700633], AGRP [rs3412352] and POMC [rs1042571] Polymorphisms with Obesity in Northern India. Mittal B, ed. Oman Med J. 2014;29(2):114-118. doi: 10.5001/omj.2014.28Srivastava A, Mittal B, Prakash J, et al. Evaluation of MC4R [rs17782313, rs17700633], AGRP [rs3412352] and POMC [rs1042571] Polymorphisms with Obesity in Northern India. Mittal B, ed. Oman Med J. 2014;29(2):114-118. doi: 10.5001/omj.2014.28Dardeno TA, Chou SH, Moon H-S, Chamberland JP, Fiorenza CG, Mantzoros CS. Leptin in human physiology and therapeutics. Front Neuroendocrinol. 2010;31(3):377-393. doi: 10.1016/j.yfrne.2010.06.002Dardeno TA, Chou SH, Moon H-S, Chamberland JP, Fiorenza CG, Mantzoros CS. Leptin in human physiology and therapeutics. Front Neuroendocrinol. 2010;31(3):377-393. doi: 10.1016/j.yfrne.2010.06.002Smith AI, Funder JW. Proopiomelanocortin Processing in the Pituitary, Central Nervous System, and Peripheral Tissues. Endocr Rev. 1988;9(1):159-179. doi: 10.1210/edrv-9-1-159Smith AI, Funder JW. Proopiomelanocortin Processing in the Pituitary, Central Nervous System, and Peripheral Tissues. Endocr Rev. 1988;9(1):159-179. doi: 10.1210/edrv-9-1-159Yang Y Structure, function and regulation of the melanocortin receptors. Eur J Pharmacol. 2011;660(1):125-130. doi: 10.1016/j.ejphar.2010.12.020.Yang Y Structure, function and regulation of the melanocortin receptors. Eur J Pharmacol. 2011;660(1):125-130. doi: 10.1016/j.ejphar.2010.12.020.Redinger RN. The pathophysiology of obesity and its clinical manifestations. Gastroenterol hepatol (NY). 2007;3(11):856-63.Redinger RN. The pathophysiology of obesity and its clinical manifestations. Gastroenterol hepatol (NY). 2007;3(11):856-63.Loos RJF, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008;40(6):768-775. doi: 10.1038/ng.140Loos RJF, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008;40(6):768-775. doi: 10.1038/ng.140Rotter I, Skonieczna-Zydecka K, Kosik-Bogacka D, et al. Relationships between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men – a preliminary study. Clin Interv Aging. 2016;11(6):1723-1732. doi: 10.2147/CIA.S120253Rotter I, Skonieczna-Zydecka K, Kosik-Bogacka D, et al. Relationships between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men – a preliminary study. Clin Interv Aging. 2016;11(6):1723-1732. doi: 10.2147/CIA.S120253Song J-Y, Song Q-Y, Wang S, et al. Physical Activity and Sedentary Behaviors Modify the Association between Melanocortin 4 Receptor Gene Variant and Obesity in Chinese Children and Adolescents. PLoS One. 2017;12(1):e0170062. doi: 10.1371/journal.pone.0170062Song J-Y, Song Q-Y, Wang S, et al. Physical Activity and Sedentary Behaviors Modify the Association between Melanocortin 4 Receptor Gene Variant and Obesity in Chinese Children and Adolescents. PLoS One. 2017;12(1):e0170062. doi: 10.1371/journal.pone.0170062Hardy R, Wills AK, Wong A, et al. Life course variations in the associations between FTO and MC4R gene variants and body size. Hum Mol Genet. 2010;19(3):545-552. doi: 10.1093/hmg/ddp504Hardy R, Wills AK, Wong A, et al. Life course variations in the associations between FTO and MC4R gene variants and body size. Hum Mol Genet. 2010;19(3):545-552. doi: 10.1093/hmg/ddp504Liu G, Zhu H, Lagou V, et al. Common Variants Near Melanocortin 4 Receptor Are Associated with General and Visceral Adiposity in European- and African-American Youth. J Pediatr. 2010;156(4):598-605.e1. doi: 10.1016/j.jpeds.2009.10.037Liu G, Zhu H, Lagou V, et al. Common Variants Near Melanocortin 4 Receptor Are Associated with General and Visceral Adiposity in European- and African-American Youth. J Pediatr. 2010;156(4):598-605.e1. doi: 10.1016/j.jpeds.2009.10.037Corella D, Ortega-Azorín C, Sorlí JV, et al. Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption. PLoS One. 2012;7(12):e52344. doi: 10.1371/journal.pone.0052344Corella D, Ortega-Azorín C, Sorlí JV, et al. Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption. PLoS One. 2012;7(12):e52344. doi: 10.1371/journal.pone.0052344Adan RAH, Tiesjema B, Hillebrand JJG, et al. The MC4 receptor and control of appetite. Br J Pharmacol. 2006;149(7):815-827. doi: 10.1038/sj.bjp.0706929Adan RAH, Tiesjema B, Hillebrand JJG, et al. The MC4 receptor and control of appetite. Br J Pharmacol. 2006;149(7):815-827. doi: 10.1038/sj.bjp.0706929Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted Disruption of the Melanocortin-4 Receptor Results in Obesity in Mice. Cell. 1997;88(1):131-141. doi: 10.1016/S0092-8674(00)81865-6Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted Disruption of the Melanocortin-4 Receptor Results in Obesity in Mice. Cell. 1997;88(1):131-141. doi: 10.1016/S0092-8674(00)81865-6Marsh DJ, Hollopeter G, Huszar D, et al. Response of melanocortin–4 receptor–deficient mice to anorectic and orexigenic peptides. Nat Genet. 1999;21(1):119-122. doi: 10.1038/5070Marsh DJ, Hollopeter G, Huszar D, et al. Response of melanocortin–4 receptor–deficient mice to anorectic and orexigenic peptides. Nat Genet. 1999;21(1):119-122. doi: 10.1038/5070Ghamari-Langroudi M, Digby GJ, Sebag JA, et al. G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature. 2015;520(7545):94-98. doi: 10.1038/nature14051Ghamari-Langroudi M, Digby GJ, Sebag JA, et al. G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature. 2015;520(7545):94-98. doi: 10.1038/nature14051Morgan DA, McDaniel LN, Yin T, et al. Regulation of Glucose Tolerance and Sympathetic Activity by MC4R Signaling in the Lateral Hypothalamus. Diabetes. 2015;64(6):1976-1987. doi: 10.2337/db14-1257Morgan DA, McDaniel LN, Yin T, et al. Regulation of Glucose Tolerance and Sympathetic Activity by MC4R Signaling in the Lateral Hypothalamus. Diabetes. 2015;64(6):1976-1987. doi: 10.2337/db14-1257Balthasar N, Dalgaard LT, Lee CE, et al. Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure. Cell. 2005;123(3):493-505. doi: 10.1016/j.cell.2005.08.035Balthasar N, Dalgaard LT, Lee CE, et al. Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure. Cell. 2005;123(3):493-505. doi: 10.1016/j.cell.2005.08.035Martinelli CE, Keogh JM, Greenfield JR, et al. Obesity due to Melanocortin 4 Receptor (MC4R) Deficiency Is Associated with Increased Linear Growth and Final Height, Fasting Hyperinsulinemia, and Incompletely Suppressed Growth Hormone Secretion. J Clin Endocrinol Metab. 2011;96(1):E181-E188. doi: 10.1210/jc.2010-1369Martinelli CE, Keogh JM, Greenfield JR, et al. Obesity due to Melanocortin 4 Receptor (MC4R) Deficiency Is Associated with Increased Linear Growth and Final Height, Fasting Hyperinsulinemia, and Incompletely Suppressed Growth Hormone Secretion. J Clin Endocrinol Metab. 2011;96(1):E181-E188. doi: 10.1210/jc.2010-1369Devesa J, Almengló C, Devesa P. Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth? Clin Med Insights Endocrinol Diabetes. 2016;9:47-71. doi: 10.4137/CMED.S38201Devesa J, Almengló C, Devesa P. Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth? Clin Med Insights Endocrinol Diabetes. 2016;9:47-71. doi: 10.4137/CMED.S38201Scacchi M, Pincelli AI, Cavagnini F Growth hormone in obesity. Int J Obes. 1999; 23(3):260-7. 1999;23(3):260-271. doi: 10.1038/SJ.IJO.0800807Scacchi M, Pincelli AI, Cavagnini F Growth hormone in obesity. Int J Obes. 1999; 23(3):260-7. 1999;23(3):260-271. doi: 10.1038/SJ.IJO.0800807Thearle MS, Muller YL, Hanson RL, et al. Greater Impact of Melanocortin-4 Receptor Deficiency on Rates of Growth and Risk of Type 2 Diabetes During Childhood Compared With Adulthood in Pima Indians. Diabetes. 2012;61(1):250-257. doi: 10.2337/db11-0708Thearle MS, Muller YL, Hanson RL, et al. Greater Impact of Melanocortin-4 Receptor Deficiency on Rates of Growth and Risk of Type 2 Diabetes During Childhood Compared With Adulthood in Pima Indians. Diabetes. 2012;61(1):250-257. doi: 10.2337/db11-0708Tan HY, Steyn FJ, Huang L, et al. Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone. J Physiol. 2016;594(24):7309-7326. doi: 10.1113/JP272770Tan HY, Steyn FJ, Huang L, et al. Hyperphagia in male melanocortin 4 receptor deficient mice promotes growth independently of growth hormone. J Physiol. 2016;594(24):7309-7326. doi: 10.1113/JP272770

The authors declare that there are no conflicts of interest present.