目的:一些研究已经调查了神经性厌食症与调节5-羟色胺神经传递的基因多态性之间的关联。重点研究了5-HTR2A的rs6311多态性。然而,这些研究的不一致结果和现有荟萃分析的矛盾结论使对可能关联的理解变得复杂.我们更新了这些结果,并评估了其他5-羟色胺受体基因多态性在神经性厌食症中的参与。
方法:遵守PRISMA指南,我们检索了1997年至2022年发表的关于神经性厌食症和5-羟色胺调节基因的研究,选择了与受体基因有关的研究,并对20项关于5-HTR2Ars6311多态性和5-HTR2Crs6318多态性的候选基因研究的结果进行了荟萃分析.
结果:目前的分析揭示了5-HTR2Ars6311多态性的关联,带有G和A等位基因,在18项研究中(2049名患者,2877个控件;A与G等位基因,赔率比=1.24;95%置信区间=1.06-1.47;p=0.009)。然而,在地理分组之后,一个协会只出现在南欧地区,涉及五项研究(722名患者,773个控件;A与G等位基因,赔率比=1.82;95%置信区间=1.41-2.37;p<0.00001)。在三项研究中,未观察到5-HTR2Crs6318多态性的关联。
结论:迄今为止,5-HTR2Ars6311多态性参与神经性厌食症的病理生理学似乎仅限于特定的遗传和/或环境背景,而5-HTR2Crs6318多态性似乎被排除在外。全基因组关联研究和表观遗传学研究可能会提供对可能导致该疾病的遗传和环境因素的更深入的见解。
方法:III从精心设计的队列或病例对照分析研究中获得的证据。临床试验注册PROSPERO注册号:CRD42021246122。
OBJECTIVE: Several studies have investigated the association between anorexia nervosa and polymorphisms of genes regulating serotonin neurotransmission, with a focus on the rs6311 polymorphism of 5-HTR2A. However, inconsistent results of these studies and conflicting conclusions of existing meta-analyses complicate the understanding of a possible association. We have updated these results and evaluated the involvement of other serotonin receptor gene polymorphisms in anorexia nervosa.
METHODS: Adhering to PRISMA guidelines, we have searched studies on anorexia nervosa and serotonin-regulating genes published from 1997 to 2022, selected those concerning receptor genes and meta-analyzed the results from twenty candidate gene studies on the 5-HTR2A rs6311 polymorphism and the 5-HTR2C rs6318 polymorphism.
RESULTS: Present analyses reveal an association for the 5-HTR2A rs6311 polymorphism, with G and A alleles, across eighteen studies (2049 patients, 2877 controls; A vs. G allele, Odds Ratio = 1.24; 95% Confidence Interval = 1.06-1.47; p = 0.009). However, after geographic subgrouping, an association emerged only in a Southern European area, involving five studies (722 patients, 773 controls; A vs. G allele, Odds Ratio = 1.82; 95% Confidence Interval = 1.41-2.37; p < 0.00001). No association was observed for the 5-HTR2C rs6318 polymorphism across three studies.
CONCLUSIONS: To date, the involvement in the pathophysiology of anorexia nervosa of the 5-HTR2A rs6311 polymorphism appears limited to a specific genetic and/or environmental context, while that of the 5-HTR2C rs6318 polymorphism seems excluded. Genome-wide association studies and epigenetic studies will likely offer deeper insights of genetic and environmental factors possibly contributing to the disorder.
METHODS: III Evidence obtained from well-designed cohort or case-control analytic studies. Clinical trial registration PROSPERO registration number: CRD42021246122.