Department of Clinical Chemistry and Pathobiochemistry, School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
Psychopharmacology (Berl). 2023 Apr;240(4):899-908. doi: 10.1007/s00213-023-06331-9. Epub 2023 Feb 9.
Weight gain is a frequent side effect of treatment with SGAs (second-generation antipsychotics) and a leading cause for nonadherence. Several candidate genes have been identified that could influence the amount of AIWG (antipsychotic-induced weight gain). The polymorphism rs17782313 near the MC4R (human melanocortin 4 receptor gene) was strongly associated with obesity in a large scale GWAS (genome wide association study), yet previous studies investigating its impact on AIWG did not lead to a definite conclusion regarding its effect. In particular, they were all relatively short and had a naturalistic design.
We therefore examined the influence of the rs17782313 polymorphism on SGA-related weight gain.
Participants of a multicenter randomized, controlled, double-blind study comparing two treatment strategies in individuals with schizophrenia or schizoaffective disorder were genotyped using a rapid-cycle polymerase chain reaction. Up to 252 individuals completed the first 2 weeks (phase I), 212 the entire 8 weeks (hence 'completers'). Patients received either amisulpride or olanzapine or both consecutively. Thirty-seven had their first episode. Weight gain occurring in different genotypes was statistically compared and confounding factors were adjusted by stepwise multiple linear regression. A correction for multiple testing was included.
Within 212 'completers', carriers of the C allele had a higher absolute weight gain than those homozygous for the T allele (2.6 kg vs. 1.2 kg), though this observation was not significant (P = 0.063). In the amisulpride subpopulation, this association appeared stronger and reached significance (2.5 kg vs. 0.7 kg, P = 0.043), though failed to remain significant after correction for multiple testing. A stepwise multiple linear regression showed a significant association in both the whole study population (P < 0.001) and the amisulpride subpopulation (P < 0.001).
Our results indicate that the rs17782313 polymorphism might influence antipsychotic-induced weight gain and therefore confirm some of the earlier conclusions.
体重增加是第二代抗精神病药物（SGAs）治疗的常见副作用，也是导致不依从的主要原因。已经确定了几个候选基因，这些基因可能会影响 AIWG（抗精神病药引起的体重增加）的数量。在一项大规模全基因组关联研究（GWAS）中，MC4R（人类黑素皮质素 4 受体基因）附近的 rs17782313 多态性与肥胖密切相关，但之前研究其对 AIWG 影响的研究并未得出其确切结论。特别是，它们都相对较短，且采用自然设计。
我们因此研究了 rs17782313 多态性对 SGA 相关体重增加的影响。
使用快速循环聚合酶链反应对接受精神分裂症或分裂情感障碍的多中心随机、对照、双盲研究的参与者进行基因分型。多达 252 名患者完成了前 2 周（第 I 阶段），212 名患者完成了整个 8 周（因此为“完成者”）。患者连续接受氨磺必利或奥氮平或两者联合治疗。37 例患者为首发。通过逐步多元线性回归对不同基因型的体重增加进行统计学比较，并调整混杂因素。进行了多次测试校正。
在 212 名“完成者”中，C 等位基因携带者的体重绝对增加量高于 TT 纯合子（2.6 公斤对 1.2 公斤），尽管这一观察结果无统计学意义（P = 0.063）。在氨磺必利亚组中，这种关联似乎更强且具有统计学意义（2.5 公斤对 0.7 公斤，P = 0.043），但在进行多次测试校正后，这一结果不再具有统计学意义。逐步多元线性回归显示，在整个研究人群（P < 0.001）和氨磺必利亚组（P < 0.001）中均存在显著关联。
我们的结果表明，rs17782313 多态性可能会影响抗精神病药引起的体重增加，从而证实了一些早期结论。
