Smoothelin is a specific cytoskeletal protein that is associated with smooth muscle cells. The human SMTN gene encodes smoothelin-A and smoothelin-B, and studies using SMTN gene knockout mice have demonstrated that these animals develop hypertension. The aim of the present study was to investigate the association between the human SMTN gene and essential hypertension (EH) using a haplotype-based case-control study. This is the first study to assess the association between essential hypertension and this gene. A total of 255 EH patients and 225 controls were genotyped for the five single-nucleotide polymorphisms (rs2074738, rs5997872, rs56095120, rs9621187 and rs10304) used as genetic markers for the human SMTN gene. Data were analyzed for three separate groups: total subjects, men and women. Although there were no differences for genotype distributions, or the dominant and recessive model distributions noted for total subjects, men and women for all of the SNPs selected for the present study, for the total subjects group, the frequency of the G-C-A-C haplotype constructed with rs2074738-rs5997872-rs56095120-rs9621187 was significantly lower in the essential hypertension patients than in the controls (P = 0.002). The G-C-A-C haplotype appears to be a useful protective marker of essential hypertension in Japanese, and the SMTN gene might also be a genetic marker for essential hypertension.
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