Genetic variation in 25-OH vitamin D 1alpha hydroxylase (CYP27B1) is associated with congestive heart failure in patients with hypertension

Abstract

Background: Dysregulation of Vitamin D homeostasis can alter myocardial contractility and cardiac morphology in animal models of congestive heart failure. Clinical studies also reveal that low vitamin D status is associated with increased risk of heart failure. Objective: Quantify association between genetic variation in Vitamin-D signaling and congestive heart failure in hypertensive human subjects in a population-based Biobank. Design: Retrospective genotype-phenotype association study, using five candidate genes, two of which were selected due to their role in Vitamin D-dependent signaling. Methods: The electronic medical records of the 20,000 subjects from the Marshfield Clinic Personalized Medicine Research Project (PMRP) were interrogated for representative cases of hypertension and congestive heart failure, along with age- and genderfrequency matched controls, based on the presence or absence of diagnostic codes. Further classification was made during routine echocardiography. Single nucleotide polymorphisms (SNPs) in five candidate genes were characterized. Analyses included logistic regression to adjust for covariates. Results: In the context of hypertension, a single nucleotide polymorphism (rs4646536) in the sixth intron of CYP27B1 was associated with congestive heart failure. Subjects who were homozygous for the C allele were more likely to have co-morbid heart failure than hypertensive subjects with either the TT or TC genotype (O.R. 2.14; 95% CI 1.05- 4.39). Also, a SNP (rs4646537) in the eighth intron of CYP27B1 was associated with protection from hypertension. Subjects who were heterozygous for the minor C allele were less likely associated with hypertension than control subjects (O.R. 0.35; 95% CI 0.13-0.91). Conclusions: Genetic variation in Vitamin D biosynthesis is associated with an increased risk of congestive heart failure in patients who have hypertension