Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden)

• Published in: PloS one Vol. 13; no. 12; p. e0209268
• Main Authors: Björk, Anne, Mellström, Dan, Ohlsson, Claes, Karlsson, Magnus, Mallmin, Hans, Johansson, Gunnar, Ljunggren, Östen, Kindmark, Andreas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2018; Public Library of Science (PLoS)
• Subjects: 25-Hydroxyvitamin D; Aged; Aged, 80 and over; Basic Medicine; Biology and Life Sciences; Biomarkers - blood; Bone density; Bone Density - genetics; Bone mineral density; Bone surgery; Bone turnover; Calcifediol - blood; Calcium; Calcium - blood; Calcium homeostasis; Calcium phosphates; Cholestanetriol 26-Monooxygenase - genetics; Clinical Medicine; Cohort Studies; Cooperation; Correlation; Cytochrome P450 Family 2 - genetics; Dairy products; Deoxyribonucleic acid; Diabetes; Dietary supplements; DNA; Endocrinology and Diabetes; Endokrinologi och diabetes; Enzymes; Fibroblast growth factor 23; Fibroblast Growth Factors - blood; Fibroblasts; Fractures; Fractures, Bone - blood; Fractures, Bone - genetics; Genetic diversity; Genetic variance; Genomes; Genotyping; Geriatrics; Growth factors; Haplotypes; Homeostasis; Humans; Hydroxylase; Incidence; Klinisk medicin; Male; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicine; Medicine and Health Sciences; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Metabolism; Metabolites; Mortality; Nutrition research; Older people; Orthopedics; Ortopedi; Osteoporosis; Parathyroid; Parathyroid hormone; Parathyroid Hormone - blood; Phosphates; Phosphates - blood; Physical sciences; Polymorphism, Single Nucleotide; Population studies; Prospective Studies; Serum levels; Single-nucleotide polymorphism; Standardization; Studies; Sweden; Tagging; Vitamin D; Vitamin D3; Vitamin deficiency; Sweden; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0209268

Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD). Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69-81), were analyzed. Genotyping was performed for eight SNPs covering the CYP2R1 gene in 2868 men with available samples of DNA. Subjects were followed up concerning incidence of fracture during five years. There was a significant genetic association with circulating levels of 25(OH)D (4.6-18.5% difference in mean values between SNP alleles), but there were no correlations with levels of calcium, phosphate, PTH or FGF23 for any genetic variant. No differences were found in fracture incidence between the variants. There was an inverse relationship between lower BMD and concomitant higher 25(OH)D for three of the haplotypes (p < 0.005). Common variants in the CYP2R1 gene encoding Vitamin D 25-hydroxylase correlate with levels of circulating 25(OH)D but do not otherwise associate with measures of calcium and phosphate homeostasis. Presence of the specific haplotypes may be an indicator of risk for low 25(OH)D levels, and may in addition be correlated to bone mineral density.