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).


METHODS
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.
From the Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (JPR); the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (EDM); the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (ES); and the Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN (JSP and PLL). reisjp@mail.nih.gov.
Jared P
JP
Reis
From the Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (JPR); the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (EDM); the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (ES); and the Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN (JSP and PLL).
Erin D
ED
Michos
From the Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (JPR); the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (EDM); the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (ES); and the Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN (JSP and PLL).
Elizabeth
E
Selvin
From the Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (JPR); the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (EDM); the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (ES); and the Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN (JSP and PLL).
James S
JS
Pankow
From the Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (JPR); the Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (EDM); the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (ES); and the Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN (JSP and PLL).
Pamela L
PL
Lutsey
D000368:Aged; D050197:Atherosclerosis; D001682:Biological Availability; D044383:Black People / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D001827:Body Height; D015992:Body Mass Index; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D044465:White People / Q000235:genetics
D001786:Blood Glucose; D014280:Triglycerides; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D002784:Cholesterol; C104450:25-hydroxyvitamin D; D003404:Creatinine
cohort study; diabetes; race; vitamin D binding protein polymorphisms