Common Variation in Vitamin D Pathway Genes Predicts Circulating 25-Hydroxyvitamin D Levels among African Americans

Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions

Overweight children have higher circulating hepcidin concentrations and lower iron status but have dietary iron intakes and bioavailability comparable with normal weight children

BACKGROUND: Obesity increases the risk for iron deficiency, but the underlying mechanism is unclear. It is possible that overweight individuals may have lower dietary iron intake and/or bioavailability. Alternatively, obesity-related inflammation may increase hepcidin concentrations and reduce iron availability. Circulating hepcidin levels have not been compared in normal weight vs overweight individuals. OBJECTIVE: The objective of this study was to compare iron status, dietary iron intake and bioavailability, as well as circulating levels of hepcidin, leptin and interleukin-6 (IL-6), in overweight vs normal weight children. DESIGN: In 6-14-year-old normal and overweight children (n=121), we measured dietary iron intake, estimated iron bioavailability and determined body mass index s.d. scores (BMI-SDS). In all children (n=121), we measured fasting serum ferritin, soluble transferrin receptor (sTfR), C-reactive protein (CRP) and leptin; in a subsample, we measured IL-6 (n=68) and serum hepcidin (n=30). RESULTS: There were no significant differences in dietary iron intake or bioavailability comparing normal and overweight children. The prevalence of iron-deficient erythropoiesis (an increased sTfR concentration) was significantly higher in the overweight than in the normal weight children (20 vs 6%, P=0.022, with sTfR concentrations of 4.40+/-0.77 and 3.94+/-0.88 mg l(-1), respectively, P=0.010). Serum hepcidin levels were significantly higher in the overweight children (P=0.001). BMI-SDS significantly correlated with sTfR (P=0.009), serum hepcidin (P=0.005) and the three measures of subclinical inflammation, namely CRP (P<0.001), IL-6 (P<0.001) and leptin (P<0.001). In a multiple regression model, serum hepcidin was correlated with BMI-SDS (P=0.020) and body iron (P=0.029), but not with the inflammatory markers. CONCLUSION: Our findings indicate that there is reduced iron availability for erythropoiesis in overweight children and that this is unlikely due to low dietary iron supply but rather due to hepcidin-mediated reduced iron absorption and/or increased iron sequestration