The role of genetic factors in predicting results of obesity treatment with sibutramine – serotonin-norepinephrine reuptake inhibitor

Aim. To study the influence of SERT and GNB3 gene polymorphisms on the results of the treatment of obesity by serotonin-norepinephrine reuptake inhibitors.

Methods. Patients who didn’t achieve significant weight loss in 3 month period during PrimaVera Study were selected for the genetic evaluation and compared with the group of “effective treatment”. The study included 66 patients (57 females and 9 males), mean age 39.29 ± 12.64 years, who received Reduxin (sibutramine + MCC) at the dose of 10 mg. Term follow-up was 3 months. Clinical examination and determination of biochemical parameters was performed at baseline and at the end of the observation period. In order to assess the type of eating behavior and identify hidden depressions a validated questionnaire was used (questionnaire "The types of eating disorders» (DEBQ), Beck Depression Scale). Also conducted a genetic study to assess SERT and GBN3 gene polymorphisms.

Results. In the second group presence of S-allele SERT-gene was significantly associated with higher rates of external type of eating behavior. A statistically significant correlation between the genotype or allele of either body weight, rates of blood pressure, heart rate and cholesterol have not been found. In the first group there was a statistically significant association of S-allele carrier with less weight loss -2.8 kg (compared to l-allele) and higher rates at baseline glucose 5.38 ± 0.63 mmol / l (compared to L-allele of -3.28 kg and 5.04 ± 0.91 mmol / l).

In the study of GBN3 polymorphism in the second group among CC genotype carriers there were higher levels of systolic blood pressure (SBP) before treatment (129.27 ± 9.16 mmHg), SBP and diastolic blood pressure after 3 months of treatment (127.36 ± 8.16 and 78.36 ± 4.3 mmHg) compared with CT genotype (117.27 ± 12.5; 115.45 ± 10.6; 72.91 ± 6.0 mm Hg, respectively) (p <0.05). Also among the carriers of C-allele there were more severe manifestations of depressive syndrome in comparison with T-allele carriers.

Conclusion. Among the carriers of S-allele of SERT gene body weight loss during Reduxin treatment was lower than among the carriers of the L-allele; among the carriers of CC genotype of GBN3 gene higher blood pressure was higher at baseline and during Reduxin treatment, as well as more severe symptoms of a depressive syndrome.

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