Genetic Variant Coding for Iron Regulatory Protein HFE Contributes to Hypertension, the TAMRISK Study

Iron is essential for body homeostasis, but iron overload may lead to metabolic abnormalities and thus increase the risk for atherosclerosis and many other diseases. Major histocompatibility complex class I-like transmembrane protein (HFE) is involved in body iron metabolism. The gene coding for HFE has 3 well-known polymorphic sites of which H63D (rs1799945, C > G) has recently been associated with hypertension in a genome-wide association study (GWAS) study. In the present study, we wanted to clarify whether the genetic variant associates with hypertension in a Finnish cohort consisting of 50-year-old men and women. The study included 399 hypertensive cases and 751 controls from the Tampere adult population cardiovascular risk study (TAMRISK) cohort. Genotyping of polymorphisms was done by polymerase chain reaction using DNAs extracted from buccal swabs. We found that individuals with the mutated form of the H63D polymorphic site (G-allele) had a 1.4-fold risk (P = 0.037, 95% confidence interval [CI] 1.02-1.89) for hypertension at the age of 50 years compared with the CC genotype carriers. When obese subjects (body mass index > 30 kg/m²) were analyzed in their own group, the risk for hypertension was even stronger (odds ratio 4.15, P < 0.001, 95% CI 1.98-8.68). We also noticed that the blood pressure (BP) readings were higher in those with the minor G-allele when compared to ones having a normal genotype already at the age of 35 years. Means of systolic/diastolic BPs were 127/81 mm Hg for CC and 131/83 mm Hg for CG + GG groups (P < 0.001 for systolic and P = 0.005 for diastolic pressure). In conclusion, HFE genetic variant H63D was associated with essential hypertension in Finnish subjects from the TAMRISK cohort confirming a previous GWAS study. The effect of this SNP on BP was also confirmed from a longitudinal study.