Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
J Steroid Biochem Mol Biol. 2010 Oct;122(4):186-92. doi: 10.1016/j.jsbmb.2010.06.013. Epub 2010 Jun 26.
Vitamin D deficiency is associated with many adverse health outcomes. There are several well established environmental predictors of vitamin D concentrations, yet studies of the genetic determinants of vitamin D concentrations are in their infancy. Our objective was to conduct a pilot genome-wide association (GWA) study of 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25OHD) concentrations in a subset of 229 Hispanic subjects, followed by replication genotyping of 50 single nucleotide polymorphisms (SNPs) in the entire sample of 1190 Hispanics from San Antonio, Texas and San Luis Valley, Colorado. Of the 309,200 SNPs that met all quality control criteria, three SNPs in high linkage disequilibrium (LD) with each other were significantly associated with 1,25OHD (rs6680429, rs9970802, and rs10889028) at a Bonferroni corrected P-value threshold of 1.62 × 10(-7), however none met the threshold for 25[OH]D. Of the 50 SNPs selected for replication genotyping, five for 25[OH]D (rs2806508, rs10141935, rs4778359, rs1507023, and rs9937918) and eight for 1,25OHD (rs6680429, rs1348864, rs4559029, rs12667374, rs7781309, rs10505337, rs2486443, and rs2154175) were replicated in the entire sample of Hispanics (P<0.01). In conclusion, we identified several SNPs that were associated with vitamin D metabolite concentrations in Hispanics. These candidate polymorphisms merit further investigation in independent populations and other ethnicities.
维生素 D 缺乏与许多不良健康后果有关。有几种已被充分证实的环境因素可以预测维生素 D 浓度，但对维生素 D 浓度的遗传决定因素的研究仍处于起步阶段。我们的目的是在德克萨斯州圣安东尼奥和科罗拉多州圣路易斯谷的 1190 名西班牙裔人群中，对 25-羟维生素 D（25[OH]D）和 1,25-二羟维生素 D（1,25OHD）浓度进行 25 名西班牙裔受试者的全基因组关联（GWA）研究的先导试验，随后对整个样本中的 50 个单核苷酸多态性（SNP）进行复制基因分型。在符合所有质量控制标准的 309,200 个 SNP 中，三个彼此之间高度连锁不平衡（LD）的 SNP 与 1,25OHD（rs6680429、rs9970802 和 rs10889028）显著相关，在 Bonferroni 校正的 P 值阈值为 1.62×10(-7)，但没有一个 SNP 达到 25[OH]D 的阈值。在选择用于复制基因分型的 50 个 SNP 中，有 5 个与 25[OH]D（rs2806508、rs10141935、rs4778359、rs1507023 和 rs9937918）相关，8 个与 1,25OHD（rs6680429、rs1348864、rs4559029、rs12667374、rs7781309、rs10505337、rs2486443 和 rs2154175）在整个西班牙裔人群中得到了复制（P<0.01）。总之，我们在西班牙裔人群中发现了一些与维生素 D 代谢物浓度相关的 SNP。这些候选多态性值得在独立人群和其他种族中进一步研究。
