Race, Vitamin D-binding Protein Gene Polymorphisms, 25-hydroxyvitamin D, and Incident Diabetes: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Low 25-hydroxyvitamin D [25(OH)D] is associated with diabetes, but few studies have examined racially diverse populations while also accounting for key vitamin D-binding protein (DBP) gene polymorphisms.

Objective: We sought to evaluate whether the association between 25(OH)D and incident diabetes varied by race and important DBP single nucleotide polymorphisms (SNPs).

Design: We studied 10,222 adults (8120 whites, 2102 blacks) aged 46-70 y at baseline (1990-1992) from the ARIC (Atherosclerosis Risk in Communities) Study with follow-up for incident diabetes ascertained during study visits conducted in 1993-1995 and 1996-1998. Adjusted HRs and their 95% CIs for diabetes were estimated according to 25(OH)D status.

Results: During follow-up there were 750 incident cases of diabetes. The association of 25(OH)D with diabetes varied by race (P-interaction = 0.004). Among whites, the adjusted HR for diabetes corresponding to each additional SD higher 25(OH)D concentration (21.3 nmol/L) was 0.95 (95% CI: 0.91, 0.99). No significant association was observed among blacks (HR: 1.06; 95% CI: 0.99, 1.14). There was evidence that the A allele at rs4588 and the T allele at rs7041, which are reported to be associated with high and low DBP concentrations, respectively, modified the association between 25(OH)D and diabetes among whites (P-interaction < 0.05 for both) but not blacks (P-interaction > 0.50 for both).

Conclusions: In this large, community-based study, low 25(OH)D concentrations were associated with diabetes among whites but not blacks. Interactions by key DBP SNPs varied between genotypes associated with either high or low DBP concentrations among whites but not blacks. Nevertheless, the findings from this prospective study suggest that there are important differences in the association of 25(OH)D with incident diabetes between white and black adults.