AGTR1基因与PPARγ基因多态性对非酒精性脂肪性肝病风险的相互作用

Interaction Between AGTR1 and PPARγ Gene Polymorphisms on the Risk of Nonalcoholic Fatty Liver Disease.

作者信息

Zhu Peifu, Lu Honghong, Jing Yang, Zhou Hui, Ding Yi, Wang Jie, Guo Daoxia, Guo Zhirong, Dong Chen

机构信息

1 Zhangjiagang First People's Hospital, Suzhou, China.

2 Suzhou Shili Hospital, Suzhou, China.

出版信息

Genet Test Mol Biomarkers. 2019 Mar;23(3):166-175. doi: 10.1089/gtmb.2018.0203. Epub 2019 Feb 22.

DOI:10.1089/gtmb.2018.0203

PMID:30793973

Abstract

AIMS

Nonalcoholic fatty liver disease (NAFLD) is an important public health issue worldwide. Several recent studies have reported that peroxisome proliferator-activated receptor-γ (PPARγ) and angiotensin II type 1 receptor (AGTR1) variants are associated with NAFLD occurrence, but the results have been inconsistent. The aim of this study was to analyze the interactions between PPARγ and AGTR1 polymorphisms and their associations with NAFLD in Chinese adults.

METHODS

Seven single nucleotide polymorphisms (SNPs) of the PPARγ gene and 5 SNPs of the AGTR1 gene were selected and genotyped in 1591 unrelated Chinese adults. The SNPAssoc package of R was used to examine the relationships between the selected SNPs and NAFLD.

RESULTS

After adjusting the covariance, the results from the overdominant model showed that participants carrying the T/C genotype of rs2638360 in AGTR1 have a decreased risk of NAFLD compared with those with T/T-C/C genotypes (odds ratio: 0.70, 95% confidence interval: 0.49-1.00). However, our results showed that none of the selected PPARγ variants were significantly associated with the risk of NAFLD after applying a false discovery rate correction. Among the 12 selected SNPs from PPARγ and AGTR1, model-based multifactor dimensionality reduction (MB-MDR) analyses for gene-gene interactions revealed that all the models were significantly associated with the increased risk of NAFLD (p < 0.05) except the 2-, 10-, 11-, and 12-locus models. Further, among the 10 SNPs negatively associated with NAFLD, the four-locus model (rs13431696 and rs3856806 in PPARγ, and rs5182, rs1492100 in ATGR1) and the five-locus model (rs9817428, rs1175543, rs13433696, and rs2920502 in PPARγ, and rs1492100 in ATGR1) were closely related with NAFLD susceptibility (p = 0.019 and p = 0.048, respectively).

CONCLUSION

Our present study suggests that interactions among multiple AGTR1 and PPARγ polymorphisms are associated with the risk of NAFLD in the Chinese population.

摘要

目的

非酒精性脂肪性肝病（NAFLD）是一个全球性的重要公共卫生问题。最近的几项研究报告称，过氧化物酶体增殖物激活受体γ（PPARγ）和血管紧张素II 1型受体（AGTR1）基因变异与NAFLD的发生有关，但结果并不一致。本研究的目的是分析PPARγ和AGTR1基因多态性之间的相互作用及其与中国成年人NAFLD的关联。

方法

选择PPARγ基因的7个单核苷酸多态性（SNP）和AGTR1基因的5个SNP，并对1591名无亲缘关系的中国成年人进行基因分型。使用R语言的SNPAssoc软件包来检验所选SNP与NAFLD之间的关系。

结果

调整协变量后，共显性模型结果显示，与携带T/T-C/C基因型的参与者相比，携带AGTR1基因rs2638360的T/C基因型的参与者患NAFLD的风险降低（优势比：0.70，95%置信区间：0.49-1.00）。然而，我们的结果显示，在应用错误发现率校正后，所选的PPARγ变异均与NAFLD风险无显著关联。在从PPARγ和AGTR1中选择的12个SNP中，基于模型的多因素降维（MB-MDR）基因-基因相互作用分析显示，除2位点、10位点、11位点和12位点模型外，所有模型均与NAFLD风险增加显著相关（p<0.05）。此外，在与NAFLD呈负相关的10个SNP中，四位点模型（PPARγ中的rs13431696和rs3856806，以及ATGR1中的rs5182、rs1492100）和五位点模型（PPARγ中的rs9817428、rs1175543、rs13433696和rs2920502，以及ATGR1中的rs1492100）与NAFLD易感性密切相关（分别为p=0.019和p=0.048）。