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MC4R 单核苷酸多态性及其单倍型与肥胖风险的基因-环境相互作用。

The MC4R SNPs, their haplotypes and gene-environment interactions on the risk of obesity.

机构信息

Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China.

Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Disease Control and Prevention, Nanning, Guangxi, 530021, People's Republic of China.

出版信息

Mol Med. 2020 Aug 8;26(1):77. doi: 10.1186/s10020-020-00202-1.

Abstract

BACKGROUND

Little is known about the correlation between the melanocortin 4 receptor gene (MC4R) single nucleotide polymorphisms (SNPs) and the risk of obesity. This research sought to test the MC4R rs17782313, rs476828 and rs12970134 SNPs, their haplotypes and gene-environment interactions on the risk of obesity in the Maonan ethnic group, an isolated minority in China.

METHODS

A case-control study comprised of 1836 participants (obesity group, 858; and control group, 978) was conducted. Genotypes of the three SNPs were determined by the next-generation sequencing (NGS) technology.

RESULTS

The genotypic frequencies of the three SNPs were different between the obesity and control groups (P <  0.05 for all). The minor allelic frequency of the MC4R rs17782313C, rs476828C and rs12970134A was higher in obesity than in control groups (13.8% vs. 8.3%, P <  0.001, 17.1% vs. 10.9%, P <  0.001; and 15.5% vs. 11.5%, P <  0.001; respectively). Additionally, the dominant model of rs17782313 and rs476828 SNPs revealed an increased morbidity function on the risk of obesity (P <  0.05). A correlation between SNP-environment and the risk of obesity was also observed. The rs17782313C-rs476828C-rs12970134A haplotype was associated with high risk of obesity (OR = 1.796, 95% CI = 1.447-2.229), whereas the rs17782313T-rs476828T-rs12970134G and rs17782313T-rs476828T-rs12970134A haplotypes were associated with low risk of obesity (OR = 0.699, 95% CI = 0.586-0.834 and OR = 0.620, 95% CI = 0.416-0.925; respectively). The interactions between haplotype and waist circumference on the risk of obesity were also noted.

CONCLUSIONS

We discovered that the MC4R rs17782313, rs476828 and rs12970134 SNPs and their haplotypes were associated with the risk of obesity in the Chinese Maonan population.

摘要

背景

关于黑皮质素 4 受体基因(MC4R)单核苷酸多态性(SNPs)与肥胖风险之间的相关性,目前知之甚少。本研究旨在检验 MC4R rs17782313、rs476828 和 rs12970134SNP 及其单倍型与中国少数民族毛南族肥胖风险之间的关系。毛南族是一个孤立的少数民族。

方法

采用病例对照研究,共纳入 1836 名参与者(肥胖组 858 人,对照组 978 人)。采用下一代测序(NGS)技术检测三个 SNPs 的基因型。

结果

三个 SNPs 的基因型频率在肥胖组和对照组之间存在差异(均 P<0.05)。MC4R rs17782313C、rs476828C 和 rs12970134A 的次要等位基因频率在肥胖组中高于对照组(13.8% vs. 8.3%,P<0.001,17.1% vs. 10.9%,P<0.001;和 15.5% vs. 11.5%,P<0.001;分别)。此外,rs17782313 和 rs476828SNP 的显性模型显示出对肥胖风险的增加发病功能(P<0.05)。还观察到 SNP-环境与肥胖风险之间的相关性。rs17782313C-rs476828C-rs12970134A 单倍型与肥胖高风险相关(OR=1.796,95%CI=1.447-2.229),而 rs17782313T-rs476828T-rs12970134G 和 rs17782313T-rs476828T-rs12970134A 单倍型与肥胖低风险相关(OR=0.699,95%CI=0.586-0.834 和 OR=0.620,95%CI=0.416-0.925;分别)。还注意到单倍型与腰围之间的相互作用对肥胖风险的影响。

结论

我们发现 MC4R rs17782313、rs476828 和 rs12970134SNP 及其单倍型与中国毛南族人群的肥胖风险相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a018/7414557/9546b5d8915d/10020_2020_202_Fig1_HTML.jpg

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