台湾东部阿美族人群中血管紧张素原基因分子变异与高血压的关联。

Association between molecular variants of the angiotensinogen gene and hypertension in Amis tribes of eastern Taiwan.

作者信息

Wang Ji-Hung, Lin Chi-Mo, Wang Lih-Shinn, Lai Ning-Sheng, Chen Der-Yuan, Cherng Jaw-Ming

机构信息

Division of Cardiology, Department of Internal Medicine, Buddhist Tzu-Chi General Hospital, 707, Section 3, Chung-Yang Road, Hualien, Taiwan.

出版信息

J Formos Med Assoc. 2002 Mar;101(3):183-8.

PMID:12051013

Abstract

BACKGROUND AND PURPOSE

Molecular variants (M235T and T174M) in the angiotensinogen (AGT) gene and a mutation in the promoter region that involves the presence of an adenine (A) instead of a guanine (G) 6 bp upstream from the transcription initiation site (G-6A) have been reported to have a positive correlation with hypertension. This study evaluated the association of the M235T, T174M, and G-6A mutations of the AGT gene with hypertension in Taiwanese aboriginals.

METHODS

This case-control study recruited 107 subjects with hypertension and 96 normotensive subjects from the Amis tribes of eastern Taiwan. Genomic DNA was amplified using the polymerase chain reaction (PCR) and the PCR product was analyzed using automated sequencing.

RESULTS

The frequencies of MM, MT, and TT genotypes at amino acid 235 were different between hypertensive (1%, 13%, 86%) and normotensive subjects (0%, 30%, 70%; p = 0.008), whereas the 174 variants of the AGT gene were not different between these two groups (1%, 14%, 85% in hypertensives, 1%, 17%, 82% in normotensives; p = 0.868). The distribution of GG, GA, and AA genotypes differed between the two groups (1%, 15%, 84% in hypertensives vs 1%, 31%, 68% in normotensives; p = 0.021). The frequency of the 235T allele was higher among hypertensives than normotensives (93 vs 85%; p = 0.015) and the odds ratio for association with the 235T allele (vs 235M) in hypertensives was 2.20. The frequency of the 174M allele was not different between the two groups (1 vs 1%). The frequency of the -6A allele was higher among hypertensives (83 vs 68%; p = 0.011) and the odds ratio association of hypertension with the -6A allele (vs -6G) was 2.18. Haplotype analysis showed that the -6A-235T allelic frequencies significantly differed between the two groups (chi 2 = 1.39, P = 0.001).

CONCLUSIONS

The prevalences of the 235T and -6A variants of the AGT gene in the Amis tribes of eastern Taiwan are high and are significantly associated with hypertension, whereas the 174M variant is not. The haplotype combining the 235T and -6A variants is also associated with hypertension. The prevalences of the 235T allele and -6A allele in this study and other studies in ethnic Chinese subjects are higher than those in Japanese.

摘要

背景与目的

据报道，血管紧张素原（AGT）基因中的分子变异（M235T和T174M）以及启动子区域的一种突变（转录起始位点上游6个碱基处存在腺嘌呤（A）而非鸟嘌呤（G），即G - 6A）与高血压呈正相关。本研究评估AGT基因的M235T、T174M和G - 6A突变与台湾原住民高血压的关联。

方法

本病例对照研究从台湾东部阿美族部落招募了107例高血压患者和96例血压正常者。使用聚合酶链反应（PCR）扩增基因组DNA，并通过自动测序分析PCR产物。

结果

高血压患者（1%，13%，86%）和血压正常者（0%，30%，70%；p = 0.008）在第235位氨基酸处的MM、MT和TT基因型频率不同，而AGT基因的174位变异在两组之间无差异（高血压患者中为1%，14%，85%，血压正常者中为1%，17%，82%；p = 0.868）。两组之间GG、GA和AA基因型的分布不同（高血压患者中为1%，15%，84%，血压正常者中为1%，31%，68%；p = 0.021）。高血压患者中235T等位基因的频率高于血压正常者（93%对85%；p = 0.015），高血压患者中与235T等位基因（相对于235M）关联的优势比为2.20。两组之间174M等位基因的频率无差异（1%对1%）。高血压患者中 - 6A等位基因的频率更高（83%对68%；p = 0.011），高血压与 - 6A等位基因（相对于 - 6G）关联的优势比为2.18。单倍型分析显示两组之间 - 6A - 235T等位基因频率有显著差异（χ2 = 1.39，P = 0.001）。