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

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.