CYP27B1 as an instrument gene to investigate the causal relationship between vitamin D deficiency and obesity: a family-based study

Background Vitamin D concentrations are linked to body composition indices, particularly body fat mass. Relationships between hypovitaminosis D and obesity, described by both BMI and waist circumference, have been mentioned. We have investigated the effect of a 12-week vitamin D3 supplementation on anthropometric indices in healthy overweight and obese women. Methods In a double-blind, randomized, placebo-controlled, parallel-group trial, seventy-seven participants (age 38±8.1 years, BMI 29.8±4.1 kg/m2) were randomly allocated into two groups: vitamin D (25 μg per day as cholecalciferol) and placebo (25 μg per day as lactose) for 12 weeks. Body weight, height, waist, hip, fat mass, 25(OH) D, iPTH, and dietary intakes were measured before and after the intervention. Results Serum 25(OH)D significantly increased in the vitamin D group compared to the placebo group (38.2±32.7 nmol/L vs. 4.6±14.8 nmol/L; P<0.001) and serum iPTH concentrations were decreased by vitamin D3 supplementation (-0.26±0.57 pmol/L vs. 0.27±0.56 pmol/L; P<0.001). Supplementation with vitamin D3 caused a statistically significant decrease in body fat mass in the vitamin D group compared to the placebo group (-2.7±2.1 kg vs. -0.47±2.1 kg; P<0.001). However, body weight and waist circumference did not change significantly in both groups. A significant reverse correlation between changes in serum 25(OH) D concentrations and body fat mass was observed (r = -0.319, P = 0.005). Conclusion Among healthy overweight and obese women, increasing 25(OH) D concentrations by vitamin D3 supplementation led to body fat mass reduction. This trial is registered at clinicaltrials.gov as NCT01344161.

Epidemiological studies have linked vitamin D deficiency with the susceptibility to type 1 diabetes. Higher levels of the active metabolite 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)(2)D) could protect from immune destruction of the pancreatic beta-cells. 1 alpha,25(OH)(2)D is derived from its precursor 25-hydroxyvitamin D by the enzyme 1 alpha-hydroxylase encoded by the CYP27B1 gene and is inactivated by 24-hydroxylase encoded by the CYP24A1 gene. Our aim was to study the association between the CYP27B1 and CYP24A1 gene polymorphisms and type 1 diabetes. We studied 7,854 patients with type 1 diabetes, 8,758 control subjects from the U.K., and 2,774 affected families. We studied four CYP27B1 variants, including common polymorphisms -1260C>A (rs10877012) and +2838T>C (rs4646536) and 16 tag polymorphisms in the CYP24A1 gene. We found evidence of association with type 1 diabetes for CYP27B1 -1260 and +2838 polymorphisms, which are in perfect linkage disequilibrium. The common C allele of CYP27B1 -1260 was associated with an increased disease risk in the case-control analysis (odds ratio for the C/C genotype 1.22, P = 9.6 x 10(-4)) and in the fully independent collection of families (relative risk for the C/C genotype 1.33, P = 3.9 x 10(-3)). The combined P value for an association with type 1 diabetes was 3.8 x 10(-6). For the CYP24A1 gene, we found no evidence of association with type 1 diabetes (multilocus test, P = 0.23). The present data provide evidence that common inherited variation in the vitamin D metabolism affects susceptibility to type 1 diabetes.