title: Genetic polymorphisms of angiotensinogen and essential hypertension in a Tibetan population.
abstract: 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.
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, P.R. China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.forename: Weijun
authors.initials: W
authors.lastname: Cen
authors.forename: Chaoying
authors.initials: C
authors.lastname: Cui
authors.forename: Ciren
authors.initials: C
authors.lastname: Zhuoma
authors.forename: Dan
authors.initials: D
authors.lastname: Cai
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhou
authors.forename: Changchun
authors.initials: C
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018609:Tibet
chemical_list: D000808:Angiotensinogen