Abstract B53: Determinants of serum 25-hydroxyvitamin D levels in African American women in the AMBER Consortium

Abstract

Abstract Background: African Americans (AAs) are known to have a higher prevalence of vitamin D deficiency than European Americans (EAs). Aside from darker skin pigmentation being a major contributing factor, few studies have investigated determinants of blood levels of 25-hydroxyvitamin D (25OHD) in AA women. Recent evidence suggests that differences in levels between AAs and EAs were largely eliminated after accounting for levels of vitamin D binding protein (VDBP). In the current study, we conducted a comprehensive investigation of associations between genetic and non-genetic factors, including circulating VDBP levels, and serum 25OHD levels in AA and EA women. Study population and methods. Data and biospecimens were examined in the context of the African American Breast Cancer Risk and Epidemiology (AMBER) consortium. For this analysis, levels were measured in 1,756 healthy controls from two case-control studies in AMBER, the Carolina Breast Cancer Study (CBCS) and the Women's Circle of Health Study (WCHS), and included 909 AA and 847 EA women. Blood samples collected at the time of enrollment were used for 25OHD measurement by DiaSorin Liasion immunochemiluminometric assay and VDBP measurement by Assaypro Gc-Globulin ELISA assays. Epidemiological data were collected from questionnaires and harmonized across studies. Genotype data for 25,248 typed and imputed germline variants in vitamin D-related pathways were available as a part of exome genotyping array from AAs in the consortium. Percent of European ancestry in AAs was estimated based on genotype data of ancestry informative markers. Univariate analyses and generalized linear regression analyses were conducted to relate serum 25OHD levels with genetic and non-genetic factors and between AA and EA women. Results: AA women had markedly lower 25OHD levels than EA women (14.2 ng/ml vs. 21.1 ng/ml, p<0.0001), yet had similar levels of VDBP (344 ug/ml vs. 336 ug/ml, p=0.25), which is different from the previous study in AAs showing much lower VDBP levels in AAs than in EAs. Also different is that VDBP levels with were not affected by the two GC polymorphisms rs4588 and rs7041. In AAs, a higher percent of European ancestry was also associated with higher 25OHD levels (p=0.03). Race was the strongest determinant of 25OHD levels, followed by body mass index (BMI), physical activity (walking for exercise), season of blood collection, multivitamin use, dietary vitamin D intake, cigarette smoking and study. Accounting for VDBP levels had little impact on racial difference in 25OHD levels. In analysis of germline variants with serum 25OHD levels, none of the index genome-wide association study (GWAS) variants identified in EAs, including rs2282679 and rs7041 in GC, were significant in AAs in our study. Conclusion: VDBP levels had little impact on notable differences in blood 25OHD levels between AAs and EAs. In addition to race, obesity, season of assessment, and several lifestyle factors were also important determinants of 25OHD levels. Genetic determinants of 25OHD levels in AAs are likely different from those in EAs, which warrants further investigation. Citation Format: Song Yao, Chi-Chen Hong, Ting-Yuan David Cheng, Gary Zirpoli, Stephen A. Haddad, Katherine L. Lunetta, Elisa V. Bandera, Andrew F. Olshan, Julie R. Palmer, Christine B. Ambrosone. Determinants of serum 25-hydroxyvitamin D levels in African American women in the AMBER Consortium. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B53.