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PPARG 上游遗传变异与长期持续性肥胖的联合作用:德黑兰心脏代谢遗传研究 (TCGS)。

The joint effect of PPARG upstream genetic variation in association with long-term persistent obesity: Tehran cardio-metabolic genetic study (TCGS).

机构信息

Cellular, and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 19195-4763, Tehran, Iran.

Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Eat Weight Disord. 2021 Oct;26(7):2325-2332. doi: 10.1007/s40519-020-01063-7. Epub 2021 Jan 3.

DOI:10.1007/s40519-020-01063-7
PMID:33389720
Abstract

PURPOSE

This study is the first study that aims to assess the association between SNPs located at the PPARG gene with long term persistent obesity. In this cohort association study, all adult individuals who had at least three consecutive phases of BMI (at least nine years) in Tehran genetic Cardio-metabolic Study (TCGS) were included.

METHODS

Individuals who always had 30 ≤ BMI < 35 and individuals who always had 20 < BMI ≤ 25 were assigned to the long-term persistent obese group and persistent normal weight group, respectively. Other individuals were excluded from the study. We used four gamete rules to make SNP sets from correlated nearby SNPs and kernel machine regression to analyze the association between SNP sets and persistent obesity or normal weight.

RESULTS

The normal group consisted of 1547 individuals with the mean age of 40 years, and the obese group consisted of 1676 individuals with mean age of 48 years. Two groups had a significant difference between all measured clinical characteristics at entry time. The kernel machine result shows that nine correlated SNPs located upstream of PPARG have a significant joint effect on persistence obesity.

CONCLUSION

This is the first study on the association between PPARG variants with persistent obesity. Three of the nine associated markers were reported in previous GWAS studies to be associated with related diseases. For the studied markers in the PPARG gene, the Iranian allele frequency was near the American and European populations.

LEVEL III

Case-control analytic study.

摘要

目的

本研究旨在评估位于 PPARG 基因中的 SNP 与长期持续性肥胖之间的关联,这在该领域尚属首次。在这项队列关联研究中,所有至少参加过三次 BMI 连续检测(至少 9 年)的个体均纳入 Tehran 遗传心血管代谢研究(TCGS)。

方法

将 BMI 始终为 30≤BMI<35 的个体和 BMI 始终为 20<BMI≤25 的个体分别分配到长期持续性肥胖组和持续性正常体重组,其他个体则被排除在研究之外。我们使用了四种配子规则,从相关的附近 SNP 中构建 SNP 集,并使用核机器回归分析 SNP 集与持续性肥胖或正常体重之间的关联。

结果

正常组由 1547 名平均年龄为 40 岁的个体组成,肥胖组由 1676 名平均年龄为 48 岁的个体组成。两组在进入研究时的所有测量的临床特征方面均存在显著差异。核机器结果表明,位于 PPARG 上游的九个相关 SNP 在持久性肥胖方面存在显著的联合作用。

结论

这是首次研究 PPARG 变体与持续性肥胖之间的关联。这九个相关标记物中的三个在以前的 GWAS 研究中被报道与相关疾病有关。在所研究的 PPARG 基因标记物中,伊朗的等位基因频率与美洲和欧洲人群相近。

三级

病例对照分析研究。

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