Haplotype-based association of regulator of G-protein signaling 5 gene polymorphisms with essential hypertension and metabolic parameters in Chinese

BACKGROUND: A recent genome-wide linkage study mapped blood pressure (BP)-related loci on human chromosome 1q and identified the regulator of G-protein signaling 5 (RGS5) as a candidate for regulation of BP. Thus, we assessed the relationship between RGS5 genetic polymorphisms and essential hypertension (EH) in Chinese. METHODS: A total of 906 patients with EH and 894 age- and gender-matched normotensive (NT) controls were enrolled. Sixteen single nucleotide polymorphisms (SNPs) in RGS5 were genotyped. RESULTS: There were no significant differences in the overall distributions of the genotypic and allelic frequencies for each SNPs between the two groups. However, in haplotype analysis, significant differences for the overall distributions were noted for four haplotypes constructed by five SNPs (rs12041294C/T, rs10917690A/G, rs10917695T/C, rs10917696T/C and rs2662774G/A), viz. H(2) (C-A-C-T-A) (p=0.038), H(5) (C-G-T-T-G) (p=0.001), H(6) (T-G-C-T-A) (p=0.021) and H(12) (T-A-T-T-G) (p=0.023). Serum concentrations of high- and low-density lipoprotein cholesterol showed significant associations with haplotypes revealed by a global test (p=0.0001 and 0.0309). CONCLUSIONS: Multiple SNPs in combination in RGS5 may confer risk for hypertension. Our results also lend support for the effect of RGS5 SNPs on lipid metabolism. Further studies are warranted to find the causal SNPs in RGS5 for EH.