e20 Vitamin D associated single nucleotide polymorphisms are associated with bone mass and microarchitecture in later life: findings from the Hertfordshire Cohort Study

Abstract

Background: Adequate Vitamin D levels are a key requirement for maintenance of bone health. Vitamin D levels are influenced by dietary intake, synthesis in the skin, and metabolism. Single nucleotide polymorphisms (SNPs) in genes involved with vitamin D metabolism have been associated with variations in levels of 25-hydroxyvitamin D. Here we explore relationships between these SNPs and bone mineral density (BMD) and microarchitecture in older adults enrolled in an extensively phenotyped community-dwelling cohort (the Hertfordshire Cohort Study). Method(s): Of 2997 Hertfordshire Cohort Study participants that completed a questionnaire and venous blood sampling, 996 participants underwent Dual-energy X-ray Absorptiometry (DEXA). Blood samples were analysed for 25-hydroxyvitamin D levels by Chemiluminescence immunoassay and genotyping by KASP-determined, competitive, allele-specific, polymerase chain reaction. Genotypes of interest were RS12785878 (NADSYN1), RS10741657 (CYP2R1), RS6013897 (CYP24A1) and RS4588 (GC) and these were available for 983 of the DEXA participants. Bone microarchitecture was studied in the distal radius and tibia of the non-dominant side by pQCT (Stratec XCT2000, n=622) and HRpQCT (Xtreme CT, Scanco Medical, n=346). Result(s): Baseline mean age (years) was 64.8 and 66.4 for men and women respectively. In women the G allele for the CYP2R1 was associated with lower femoral BMD (-0.13 z-score, 95% CI -0.24, -0.02, p=0.026) after adjustment for age, BMI, social class, dietary calcium intake, activity level, cigarette and alcohol consumption, years since menopause and HRT use. No significant associations were seen between vitamin D SNPs and DXA measures in men. The NADSY1 T allele was associated with lower radius mass at the 4% slice (-0.22 zscore, 95% CI -0.40, -0.04, p=0.017), while CYP2R1 (G allele) was associated with a lower tibial fracture load across the x axis (-0.21 zscore, 95% CI -0.39, -0.03 p=0.023) in men, and GC (C allele) with lower radial cortical density at the 66% slice -0.17 z-score, 95% CI -0.33, -0.00 (p=0.045) on pQCT analysis. In women there was no significant association between pQCT parameters and varying genotype. Considering bone microarchitecture, stronger associations were seen in men than women and only with NADSYN1; in men the T allele was associated with lower radial cortical area (-0.33 z-score, 95% CI -0.56, -0.09, p=0.007), trabecular density (-0.26 z-score, 95% CI -0.50, -0.01, p=0.038) and thickness (-0.28 z-score, 95% CI -0.52, -0.03, p=0.029), as well as tibial cortical area (-0.25 z-score, 95% CI -0.46, -0.04, p=0.022). By contrast, in women, far fewer associations were seen; only NADSYN1 (T allele) was associated with significantly higher radial cortical bone mineral density (0.38 z-score, 95% CI 0.09, 0.67, p=0.010). Conclusion(s): We have found further supporting evidence of a role for SNPs coding vitamin D metabolism, NADSYN1 and CYP2R1 with bone health in older adults. In general results were stronger in men than women.