Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study.

International journal of molecular epidemiology and genetics Pub Date : 2014-02-17 eCollection Date: 2014-01-01
Wei Wang, Sue Ann Ingles, Gabriela Torres-Mejía, Mariana C Stern, Frank Z Stanczyk, Gary G Schwartz, David O Nelson, Laura Fejerman, Roger K Wolff, Martha L Slattery, Esther M John
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Abstract

Genome-wide association studies (GWAS) have identified common polymorphisms in or near GC, CYP2R1, CYP24A1, and NADSYN1/DHCR7 genes to be associated with circulating levels of 25-hydroxyvitamin D [25(OH)D] in European populations. To replicate these GWAS findings, we examined six selected polymorphisms from these regions and their relation with circulating 25(OH)D levels in 1,605 Hispanic women (629 U.S. Hispanics and 976 Mexicans) and 354 non-Hispanic White (NHW) women. We also assessed the potential interactions between these variants and known non-genetic predictors of 25(OH)D levels, including body mass index (BMI), sunlight exposure and vitamin D intake from diet and supplements. The minor alleles of the two GC polymorphisms (rs7041 and rs2282679) were significantly associated with lower 25(OH)D levels in both Hispanic and NHW women. The CYP2R1 polymorphism, rs2060793, also was significantly associated with 25(OH)D levels in both groups. We found no significant associations for the polymorphisms in the CYP24A1. In Hispanic controls, 25(OH)D levels were significantly associated with the rs12785878T and rs1790349G haplotype in the NADSYN1/DHCR7 region. Significant interactions between GC rs2282679 and BMI and between rs12785878 and time spent in outdoor activities were observed. These results provide further support for the contribution of common genetic variants to individual variability in circulating 25(OH)D levels. The observed interactions between SNPs and non-genetic factors warrant confirmation.

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遗传变异和非遗传因素预测西班牙裔和非西班牙裔白人妇女循环维生素D水平:乳腺癌健康差异研究。
全基因组关联研究(GWAS)已经发现GC、CYP2R1、CYP24A1和NADSYN1/DHCR7基因中或附近的常见多态性与欧洲人群中25-羟基维生素D [25(OH)D]的循环水平相关。为了重复GWAS的研究结果,我们在1605名西班牙裔女性(629名美国西班牙裔女性和976名墨西哥裔女性)和354名非西班牙裔白人(NHW)女性中检测了从这些区域选择的6个多态性及其与循环25(OH)D水平的关系。我们还评估了这些变异与已知的25(OH)D水平的非遗传预测因子之间的潜在相互作用,包括身体质量指数(BMI)、阳光照射和饮食和补充剂中维生素D的摄入量。两种GC多态性的次要等位基因(rs7041和rs2282679)与西班牙裔和非西班牙裔妇女较低的25(OH)D水平显著相关。CYP2R1多态性rs2060793也与两组25(OH)D水平显著相关。我们发现CYP24A1基因的多态性没有显著的相关性。在西班牙对照中,25(OH)D水平与NADSYN1/DHCR7区域的rs12785878T和rs1790349G单倍型显著相关。观察到GC rs2282679与BMI、rs12785878与户外活动时间之间存在显著交互作用。这些结果进一步支持了常见遗传变异对循环25(OH)D水平个体差异的贡献。观察到的snp与非遗传因素之间的相互作用值得证实。
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