Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension

Objective The CYP11B2 locus is an important candidate region in essential hypertension (HT). We therefore investigated CYP11B2 polymorphisms T-344C, T4986C and A6547G for association with essential HT. This included haplotype analysis and measurement of plasma aldosterone levels. Methods The three single nucleotide polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis of genomic DNA from 146 HT and 291 normotensive (NT) white subjects of Anglo-Celtic descent, in whom parental blood pressure status was the same as the subjects'. Genotype and allele frequencies in HTs and NTs were compared by chi(2) analysis. Linkage disequilibrium and haplotype frequencies were estimated by the program 'snphap'. Phenotype-genotype relationships were tested using one-way analysis of variance. Results The T-344C variant was associated with HT (chi(2) = 7.4, P= 0.0064). This association was confined to female HTs (P = 0.0061 for genotypes, P = 0.0013 for alleles). A strong association with HT was also seen for the A6547G variant (P = 0.0015), being greatest in females (P< 0.0001). No association was seen for the T4986C variant. Haplotype analysis of the three single nucleotide polymorphisms across eight different haplotype combinations showed a significant association with HT (chi(2) = 24, seven degrees of freedom, P< 0.001). No significant tracking of plasma aldosterone with genotype was observed. Conclusion The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in females of the Anglo-Celtic population studied. This was reinforced by haplotype analysis.