Cellular, and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular, and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Gene. 2022 Jan 10;807:145950. doi: 10.1016/j.gene.2021.145950. Epub 2021 Sep 2.
This population-based longitudinal study is the first investigation that assesses the association of common MC4R SNPs with the obesity-related parameters over time and determines the effect of risk alleles during the three adulthood life periods (early, middle, and late) in a large Iranian cohort, a population with a unique genetic make-up that has been understudied and relatively unexplored. We obtained the genotype of 5370 unrelated adults who participated in the ongoing Tehran Cardiometabolic Genetic Study (TCGS) cohort project for the common MC4R SNPs. Linear regression and linear mixed model analyses were performed to examine the effect of MC4R polymorphisms on maximum BMI and other obesity-related factors over time. We recognized that several SNPs associated with the maximum BMI and the increased BMI, waist circumference, and waist-hip ratio across Iranian adults over a lifetime. Interestingly, we found that rs9954571-A has a yet unreported protective role against obesity-related factors, including BMI, waist circumference, waist-hip ratio, and triglyceride level. Additionally, a survey of the impact of the MC4R risk score throughout the adulthood life periods indicated that the MC4R risk score is influenced both the elevated BMI and waist circumference only during the early adulthood period. Our findings can expand our knowledge about the MC4R genetic variant's contributions to adulthood obesity and highlight the importance of evaluating the genetic components affecting obesity over a lifetime, which could be considered for obesity clinical screening and treatment.
这项基于人群的纵向研究首次评估了常见 MC4R SNPs 与肥胖相关参数随时间的相关性，并确定了在伊朗大人群中三个成年期（早期、中期和晚期）风险等位基因的作用，该人群具有独特的遗传构成，研究相对较少且尚未得到充分探索。我们获得了参加正在进行的德黑兰心脏代谢遗传研究（TCGS）队列项目的 5370 名无关成年人的常见 MC4R SNPs 基因型。线性回归和线性混合模型分析用于检查 MC4R 多态性对最大 BMI 及其他肥胖相关因素随时间的影响。我们认识到，几个 SNP 与伊朗成年人一生中的最大 BMI 以及 BMI、腰围和腰臀比的增加有关。有趣的是，我们发现 rs9954571-A 对肥胖相关因素具有尚未报道的保护作用，包括 BMI、腰围、腰臀比和甘油三酯水平。此外，对 MC4R 风险评分在整个成年期的影响的调查表明，MC4R 风险评分仅在成年早期会影响 BMI 和腰围的升高。我们的发现可以扩展我们对 MC4R 遗传变异对成年肥胖的贡献的认识，并强调评估影响肥胖的遗传因素的重要性，这可以考虑用于肥胖的临床筛查和治疗。
