Obesity is a multifactorial disorder and requires favorable environment for its expression. However, some individuals are more prone to weight gain than others in an obesogenic environment. Thus, at individual level, who becomes overweight or obese is mostly determined by genetic factors. The current study was undertaken to explore for the first time the association of the TMEM18 rs7561317 variant with overweight/obesity and related anthropometric, metabolic, physical, and behavioral traits in a sample of Pakistani population with association between the rs7561317 and many traits was not investigated before in any population. The current study involved a total of 612 subjects including 306 overweight/obese and equal number of age- and sex-matched normal weight individuals. Obesity-related parameters were determined and the variant was genotyped by allelic discrimination assay. All the aforementioned associations were assessed by regression analyses adjusted for covariates and corrected for multiple comparisons. The results revealed a significant association of the TMEM18 rs7561317 with overweight/obese phenotype in more than one genetic model. Therefore, h-index (degree of dominance) was calculated, which indicated the recessive mode of inheritance for the above-said association. Similarly, a significant association of the rs7561317 with obesity-related anthropometric traits and clinical surrogate markers of visceral adiposity was observed. Thus, GG genotype of the rs7561317 was found to increase 1.74 times the risk of overweight/obesity in Pakistani population (OR = 1.74, 95% CI 1.210–2.496, p = 0.003) while low physical activity seemed to accentuate the TMEM18 rs7561317-associated risk of overweight/obesity (OR = 2.696, 95% CI 1.485–4.896, p = 0.004).

中文翻译：

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巴基斯坦人口样本中TMEM18基因下游rs7561317变异与超重/肥胖和相关人体测量学特征的关联。

肥胖是一种多因素疾病，需要良好的表达环境。但是，在肥胖环境中，有些人比其他人更容易体重增加。因此，在个体水平上，谁变得超重或肥胖主要取决于遗传因素。进行本研究是为了首次探索TMEM18的关联在巴基斯坦人群的样本中，rs7561317变异体具有超重/肥胖症以及相关的人体测量，代谢，身体和行为特征，并且尚未在任何人群中研究过rs7561317与许多特征之间的关联。目前的研究共涉及612名受试者，包括306名超重/肥胖者以及相等数量的年龄和性别匹配的正常体重个体。确定与肥胖有关的参数，并通过等位基因鉴别分析对变体进行基因分型。通过调整协变量并进行多次比较校正的回归分析，评估了所有上述关联。结果显示，在多个遗传模型中，TMEM18 rs7561317与超重/肥胖表型显着相关。因此，h-指数（优势度）被计算，其指示上述关联的隐性遗传模式。同样，观察到rs7561317与肥胖相关的人体测量学特征和内脏肥胖的临床替代指标之间存在显着关联。因此，发现rs7561317的GG基因型增加了超重/肥胖风险的1.74倍（OR = 1.74，95％CI 1.210–2.496，p  = 0.003），而低体力活动似乎加剧了与rs7561317相关的TMEM18超重/肥胖的风险（OR = 2.696，95％CI 1.485–4.896，p  = 0.004）。