Association Study of the Elastin Microfibril Interfacer 1 (EMILIN1) Gene in Essential Hypertension

BACKGROUND: Elastin microfibril interfacer 1 (EMILIN-1) is a negative regulator of the transforming growth factor-beta (TGF-beta) signaling, which is involved in blood pressure (BP) homeostasis. Emilin1 knockout mice display elevated BP. The aim of the present study was to assess the association between the human EMILIN1 gene and essential hypertension (EH) using a haplotype-based case-control study. METHODS: A total of 287 EH patients and 253 age-matched controls were genotyped for the five single-nucleotide polymorphisms (SNPs) used as genetic markers for the human EMILIN1 gene (rs2289408, rs2289360, rs2011616, rs2304682, and rs4665947). Data were analyzed for three separate groups: the total subjects, men, and women. RESULTS: For the total, the genotypic distribution of rs2289360, rs2011616, and rs2304682 differed significantly between control and EH (P = 0.010, P = 0.009, and P = 0.008, respectively). For the total and men, there were significant differences noted between the controls and the EH patients for both the dominant model (GG vs. AA+AG) (P = 0.006, P = 0.021, respectively), and the recessive model (AA vs. AG+GG) (P = 0.028, P = 0.038, respectively) of rs2011616. For the total and the men, logistic regression analysis indicated that the AG+GG genotype of rs2011616 was significantly higher in EH patients (P = 0.033, P = 0.043, respectively). The frequency of the G-G-T haplotype (established by rs2536512, rs2016116, rs17881426) was significantly higher in EH men (P = 0.007), and the G-A-T haplotype (established by rs2536512, rs2016116, rs17881426) was significantly higher in control men (P < 0.001). CONCLUSIONS: We confirmed that rs2289360, rs2011616, and rs2304682 in the human EMILIN1 gene, as well as the haplotype constructed using rs2536512, rs2011616, and rs17881426 are useful genetic markers of EH in Japanese men.