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肾素-血管紧张素-醛固酮系统中的基因-基因相互作用对中国汉族人群终末期肾病易感性有影响。

Gene-gene interactions in renin-angiotensin-aldosterone system contributes to end-stage renal disease susceptibility in a Han Chinese population.

作者信息

Su Sui-Lung, Yang Hsin-Yi, Wu Chia-Chao, Lee Herng-Sheng, Lin Yuh-Feng, Hsu Chi-An, Lai Ching-Huang, Lin Chin, Kao Sen-Yeong, Lu Kuo-Cheng

机构信息

School of Public Health, National Defense Medical Center, Taipei, Taiwan.

Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

出版信息

ScientificWorldJournal. 2014;2014:169798. doi: 10.1155/2014/169798. Epub 2014 Apr 13.

DOI:10.1155/2014/169798
PMID:24977181
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4003748/
Abstract

OBJECTIVE

In this study, we investigated whether RAAS gene single nucleotide polymorphisms (SNPs) and their interactions were associated with end-stage renal stage (ESRD).

METHODOLOGY AND RESULTS

This was a case-control study for 647 ESRD cases and 644 controls. AGT (M235T (rs699) and T174M (rs4762)), AGTR1 (A1166C (rs5186) and C573T (rs5182)), ACE (I/D (rs1799752) and G2350A (rs4343)), and CYP11B2 C-344T (rs1799998) were genotyped and compared between cases and controls to identify SNPs associated with ESRD susceptibility. Multifactor dimensionality reduction (MDR) was used to identify gene-gene interactions. Several RAAS genes were associated with ESRD: AGT M235T, ACE I/D, ACE G2350A, and CYP11B2 C-344T. By MDR analysis, a three-locus model (ACE ID/ACE G2350A/CYP11B2 C-344T) of gene-gene interaction was the best for predicting ESRD risk, and its maximum testing accuracy was 56.08% and maximum cross-validation consistency was 9/10. ESRD risk was higher with the simultaneous occurrence of ACE I/D DD-ACE G2350A AA. AGT, ACE, and CYP11B2 gene polymorphisms are associated with ESRD.

CONCLUSIONS

The gene-gene interaction effects of ACE I/D, ACE G2350A, and CYP11B2 C-344T polymorphisms are more important than individual factors for ESRD development among Han Chinese.

摘要

目的

在本研究中，我们调查了肾素-血管紧张素-醛固酮系统（RAAS）基因单核苷酸多态性（SNP）及其相互作用是否与终末期肾病（ESRD）相关。

方法与结果

这是一项针对647例ESRD病例和644例对照的病例对照研究。对血管紧张素原（AGT）（M235T（rs699）和T174M（rs4762））、血管紧张素Ⅱ受体1型（AGTR1）（A1166C（rs5186）和C573T（rs5182））、血管紧张素转换酶（ACE）（I/D（rs1799752）和G2350A（rs4343））以及细胞色素P450 11B2 C-344T（rs1799998）进行基因分型，并在病例组和对照组之间进行比较，以确定与ESRD易感性相关的SNP。采用多因素降维法（MDR）来识别基因-基因相互作用。几个RAAS基因与ESRD相关：AGT M235T、ACE I/D、ACE G2350A和CYP11B2 C-344T。通过MDR分析，基因-基因相互作用的三位点模型（ACE ID/ACE G2350A/CYP11B2 C-344T）对预测ESRD风险最为有效，其最大检验准确度为56.08%，最大交叉验证一致性为9/10。同时出现ACE I/D DD-ACE G2350A AA时ESRD风险更高。AGT、ACE和CYP11B2基因多态性与ESRD相关。

结论

在中国汉族人群中，ACE I/D、ACE G2350A和CYP11B2 C-344T多态性的基因-基因相互作用效应在ESRD发生中比个体因素更重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab4/4003748/347c35e58e23/TSWJ2014-169798.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab4/4003748/21a5d3a7395b/TSWJ2014-169798.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab4/4003748/347c35e58e23/TSWJ2014-169798.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab4/4003748/21a5d3a7395b/TSWJ2014-169798.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ab4/4003748/347c35e58e23/TSWJ2014-169798.002.jpg

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