Genetic variation in bone morphogenetic proteins family members (BMPs 2 and 4) and hypertension risk in middle-aged men: The TAMRISK study

Bone morphogenetic proteins (BMPs) are important regulators of iron metabolism affecting hepcidin expression. We have previously shown that 2 genetic polymorphisms in different genes (histocompatibility complex class I-like transmembrane protein, hemojuvelin) involved in the regulation of hepcidin expression pathways are associated with hypertension. In this study, we analyzed genetic variation sites in BMP2 (rs235756, rs235768) and BMP4 (rs4901474) to get more evidence linking iron metabolism to hypertension risk in the Finnish population. The study included 321 hypertensive cases and 463 controls from the Tampere Adult Population Cardiovascular Risk study cohort. Genotyping of polymorphisms was done by polymerase chain reaction using DNAs extracted from buccal swabs. We found that men carrying the GG genotype of BMP2 rs235756 (A>G) polymorphic site had a 4.09-fold risk (confidence interval [CI] 1.61–10.39, P = .003) for hypertension at the age of 50 years compared with A-allele carriers. The risk was significant in the age groups of 45 and 40 years as well. In addition, the 15-year follow-up period of the same individuals showed that carriers of the GG-genotype had also significantly higher readings of both systolic (P < .001) and diastolic (P = .01) blood pressure during the follow-up time. No significant association between BMP2 rs235768 (A>T) and hypertension was found. BMP4 polymorphic site rs4901474 (T>C) also had an effect on hypertension. CC genotype carriers had a 1.48-fold risk (CI 1.03–2.13, P = .033) for hypertension at the age of 50 years when compared with T-allele carriers. In conclusion, BMP2 polymorphic site rs235756 was associated with hypertension in Finnish men. An effect of BMP4 polymorphic site on hypertension was also found.