Ann Arbor, MI - A variant of the gene responsible for the activation of vitamin D is associated with the development of congestive heart failure in individuals with hypertension, new research shows [1]. The results confirm previous studies suggesting that vitamin D is an important player in cardiovascular health, according to researchers.

"There is a great deal of information out there now about vitamin D and how important it is for cardiovascular health," said senior investigator Dr Robert Simpson (University of Michigan, Ann Arbor, MI). "My lab was the first to study it in animals back in the early 1980s. We became interested because of information that the vitamin-D receptor existed in heart tissue. Subsequently, there have now been a number of clinical studies showing the importance of adequate vitamin-D status for human heart health."

The results of the study are published in the November 2009 issue of Pharmacogenomics.

Vitamin-D insufficiency has been linked in previous studies to increased risks of coronary heart disease. Speaking with heartwire, Simpson said that previous studies have shown vitamin-D insufficiency specifically influences the severity and progression of congestive heart failure. Because enzyme CYP27B1 is responsible for the bioactivation of vitamin D, the researchers hypothesized that individuals with heart failure would be more likely to have a genetic variant of CYP27B1, a mutation that inactivates the enzyme and subsequently reduces the conversion of vitamin D into an active hormone.

Analyzing the genetic profiles of 617 individuals, they selected functional polymorphisms from five candidate genes—CYP27B1, CYP24A1, VDR, REN, and ACE—involved in the regulation of vitamin-D production and activation. Of the 617 subjects, 205 had hypertension and congestive heart failure, 206 had hypertension alone, and 206 served as age- and gender-matched controls.

Regression analyses showed that a single nucleotide polymorphism (SNP) in CYP27B1 was associated with congestive heart failure among individuals with hypertension. Hypertensive individuals homozygous for the C allele of SNP rs4646536 had a more than twofold increased risk of congestive heart failure, report researchers (odds ratio 2.14, 95% CI 1.05-4.39).

For rs4646536, the homozygous CC genotype was present in 12.7% of individuals with hypertension and heart failure and 8.7% of those with hypertension alone.

"The results confirm other studies that show that vitamin D is important for cardiovascular health, and second, it shows that a population of patients already not capable of making sufficient vitamin D or the hormone from vitamin D might be more susceptible to heart failure," Simpson told heartwire.

Researchers are unclear of the mechanism linking rs4646536 to heart failure. It is possible that rs4646536 tags an unrecognized causative allele or that it disrupts a regulatory function withinCYP27B1. They point out that a genetic variability in the metabolism of 25(OH)D would alter the role of 25(OH)D and 1,25(OH)₂D within metabolic feedback loops responsible for regulating the hormones.

The researchers note that participants in the study were predominantly white, so further studies are needed in more diverse ethnic populations. If confirmed in other studies, Simpson said that genetic mutations of CYP27B1 would allow clinicians to potentially screen patients for risk of developing heart failure.

A National Institutes of Health-sponsored study looking at whether vitamin-D and/or omega-3 fatty-acid supplementation can reduce the risk of developing heart disease, stroke, or cancer is currently under way. Known as the Vitamin D and Omega-3 Trial (VITAL), more than 20 000 subjects are to be enrolled, and results are expected in 2014.