Family‐based Association between Allele T of rs4646536 in CYP27B1 and vitamin D deficiency

BACKGROUND: The circulating concentration of 25(OH)D is widely applied to indicate the vitamin D status, as the directly metabolic genes of 25(OH)D, CYP2R1, and CYP27B1 are associated with the concentration of 25(OH)D. However, the contributions of allelic transmission disequilibrium of single nucleotide polymorphisms (SNPs) in these genes to vitamin D deficiency remain unclear. We aimed at investigating the family‐based association between SNPs of CYP2R1 and CYP27B1 and vitamin D deficiency. METHOD: First, SNPs selected in family‐based study were screened by a pilot case‐control study. Second, allelic transmissions of the selected SNPs were investigated with family‐based study (n = 880). Finally, associations between selected SNPs and the concentration of 25(OH)D were verified in siblings (n = 120). RESULTS: The results of the pilot case‐control study indicated that both CT and TT genotypes of rs4646536 in CYP27B1 could increase the susceptibility of vitamin D deficiency when compared with CC genotype. The adjusted ORs were 2.846 (95%CI 1.312‐6.174, P = 0.008) and 2.609 (95%CI 1.197‐5.687, P = 0.016), respectively. Furthermore, the results of family‐based association test suggested that there was transmission disequilibrium for allele T of rs4646536 in vitamin D deficiency families. In addition, the concentration of 25(OH)D(3) for CC genotype was higher than CT genotype between siblings (P = 0.016). CONCLUSIONS: Transmission disequilibrium of allele T of rs4646536 is associated with vitamin D deficiency.