25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms and incident coronary heart disease among whites and blacks: The ARIC study

Background: In observational studies, low 25-hydroxyvitamin D (25(OH)D) has been associated with increased risk of coronary heart disease (CHD), and this association may vary by race. Racial differences in the frequency of vitamin D binding protein (DBP) single nucleotide polymorphisms (SNPs) might account for similar bioavailable vitamin D in blacks despite lower mean 25(OH)D. We hypothesized that the associations of low 25(OH)D with CHD risk would be stronger among whites and among persons with genotypes associated with higher DBP levels. Methods: We measured 25(OH)D by mass spectroscopy in 11,945 participants in the ARIC Study (baseline 1990-1992, mean age 57 years, 59% women, 24% black). Two DBP SNPs (rs7041; rs4588) were genotyped. We used adjusted Cox proportional hazards models to examine the association of 25(OH)D with adjudicated CHD events through December 2011. Results: Over a median of 20 years, there were 1230 incident CHD events. Whites in the lowest quintile of 25(OH)D (<17ng/ml) compared to the upper 4 quintiles had an increased risk of incident CHD (HR 1.28, 95% CI 1.05-1.56), but blacks did not (1.03, 0.82-1.28), after adjustment for demographics and behavioral/socioeconomic factors (p-interaction with race=0.22). Results among whites were no longer significant after further adjustment for potential mediators of this association (i.e. diabetes, hypertension). There was no statistically significant interaction of 25(OH)D with the DBP SNPs rs4588 (p=0.92) or rs7041 (p=0.87) in relation to CHD risk. Conclusions: Low 25(OH)D was associated with incident CHD in whites, but no interactions of 25(OH)D with key DBP genotypes was found.