Genetic Polymorphisms of Angiotensinogen and Essential Hypertension in a Tibetan Population

The human angiotensinogen gene ( AGT ) is a promising candidate for an essential hypertension-susceptibility gene. We aimed to explore the single-locus, haplotype and epistasis patterns of three polymorphisms of AGT (A−20C, A−6G and M235T) and their relation to the risk of essential hypertension in...

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Veröffentlicht in:Hypertension research 2007-11, Vol.30 (11), p.1129-1137
Hauptverfasser: Niu, Wenquan, Qi, Yue, Cen, Weijun, Cui, Chaoying, Zhuoma, Ciren, Cai, Dan, Zhou, Wenyu, Qiu, Changchun
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Sprache:eng
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Zusammenfassung:The human angiotensinogen gene ( AGT ) is a promising candidate for an essential hypertension-susceptibility gene. We aimed to explore the single-locus, haplotype and epistasis patterns of three polymorphisms of AGT (A−20C, A−6G and M235T) and their relation to the risk of essential hypertension in a Tibetan population. The three polymorphisms were genotyped in 333 essential hypertension patients and 235 healthy controls on the basis of a door-to-door cross-sectional study. Genotyping was performed using polymerase chain reaction (PCR)−restriction fragment length polymerase (RFLP) and direct sequencing techniques. The data were analyzed using the EH/EH+ program and the multifactor dimensionality reduction (MDR) method. Our single-locus analysis revealed that except for a marginal, significant association of A−20C allele distribution, no significant association between genotype and allele distributions of the A−20C, A−6G, or M235T polymorphism of AGT and essential hypertension was found. In haplotype analysis, we found that the H 1 haplotype may be the risk-conferring factor for hypertension, even after the Bonferroni correction. In epistasis analysis, we selected the final best model, which included the A−20C and A−6G polymorphisms with a strong synergistic effect. This model had a maximum testing accuracy of 0.564 and a maximum cross validation consistency of 10 out of 10 ( p =0.001). The present study thus provides evidence of a strong synergistic effect of the A−20C and A−6G polymorphisms of AGT , which were not found to be associated with essential hypertension in the single-locus analysis. Moreover, we have proposed a promising data–mining analytical method using the open-source MDR software package for detecting and characterizing gene-gene interactions.
ISSN:0916-9636
1348-4214
DOI:10.1291/hypres.30.1129