The TH (tyrosine hydroxylase) gene encodes the rate-limiting enzyme of catecholamine biosynthesis, and is involved in the pathogenesis of hypertension, but the relationship of its variants with hypertension has not been extensively studied. We designed a case-controlled study consisting of 503 HT (hypertensive) individuals and 490 NT (normotensive) individuals matched by region, age and gender to systematically investigate the association between the TH gene and hypertension. Based on the HapMap and dbSNP (where SNP is single nucleotide polymorphism) data, four SNPs, rs6356 A>G, rs6357 G>A, rs2070762 T>C and rs1800033 A>G in the TH gene were selected for genotyping. Rs1800033 was not polymorphic in our study population. No significant differences were observed for distributions of rs6356 and rs6357 between the HT and NT groups. However, both the genotype and allele frequencies of rs2070762 showed significant differences between cases and controls (P<0.001 and P=0.005 respectively). In haplotype analysis, a total of eight haplotypes were observed in the entire population and the overall frequency distributions differed significantly between the HT and NT groups. Specifically, haplotype A-A-C (rs6356-rs6357-rs2070762) occurred only in the HT group and A-G-C occurred more commonly in HT subjects than in NT subjects (P=0.003 and P=0.013 respectively). Compared with the most common haplotype A-G-T, the adjusted OR (odds ratio) was 1.83 [95% CI (confidence interval), 1.20–2.79; P=0.0049] for haplotype G-G-C and 20 (P<0.0001) for the haplotype A-A-C. Functional analysis showed that the C allele of rs2070762 functioned as an enhancer in the absence of binding by unidentified transcriptional repressor(s). These results provide evidence for an association of the functional intronic rs2070762 with essential hypertension.

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