Kuipers Allison L, Yu Shibing, Kammerer Candace M, Nestlerode Cara S, Bunker Clareann H, Patrick Alan L, Wheeler Victor W, Zhang Yingze, Zmuda Joseph M
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, A543 Crabtree Hall, Pittsburgh, PA, 15261, USA,
Calcif Tissue Int. 2015 Feb;96(2):155-9. doi: 10.1007/s00223-014-9948-2. Epub 2014 Dec 31.
The aim of the study was to determine the heritability of serum dickkopf-1 (DKK1) and its association with DKK1 polymorphisms in African ancestry subjects. Serum DKK1 was measured in 422 Afro-Caribbean men and women aged 18+ from 7 large, multi-generational families (mean family size: 60; 3,215 relative pairs). Twenty-four common single nucleotide polymorphisms (SNPs) were genotyped within an 80 kilobase-pair region encompassing the DKK1 gene. Heritability was estimated and SNPs were tested for association with serum DKK1 using variance components analysis. DKK1 mRNA expression was tested in peripheral blood of 16 individuals from each of the rs7069912 genotypes. Mean serum DKK1 was 1724.1 pg/mL and was significantly lower in women than men (P = 0.043). Residual genetic heritability of serum DKK1 was 0.4460 (P < 0.0001). Six SNPs reached nominal significance with DKK1, with rs7069912 being significant after adjustment for multiple comparisons. Two of these six SNPs represented independent association signals (rs7069912 and rs16928725), which accounted for 4.6% of the phenotypic variation in DKK1. Additionally, carriers of the rs7069912 variant had significantly greater DKK1 expression than non-carriers (P = 0.036). Serum DKK1 levels are highly heritable in the African ancestry families. Two SNPs within the DKK1 region accounted for nearly 5% of the variation in serum DKK1.
该研究的目的是确定非洲裔受试者血清中 Dickkopf-1（DKK1）的遗传力及其与 DKK1 基因多态性的关联。对来自 7 个大型多代家庭（平均家庭规模：60 人；3215 对亲属）的 422 名 18 岁及以上的非洲裔加勒比男性和女性进行了血清 DKK1 检测。在包含 DKK1 基因的 80 千碱基对区域内对 24 个常见单核苷酸多态性（SNP）进行了基因分型。使用方差成分分析估计遗传力，并测试 SNP 与血清 DKK1 的关联。对 rs7069912 各基因型的 16 名个体的外周血进行了 DKK1 mRNA 表达检测。血清 DKK1 的平均值为 1724.1 pg/mL，女性显著低于男性（P = 0.043）。血清 DKK1 的残余遗传力为 0.4460（P < 0.0001）。6 个 SNP 与 DKK1 达到名义显著性，其中 rs7069912 在多重比较校正后具有显著性。这 6 个 SNP 中的 2 个代表独立的关联信号（rs7069912 和 rs16928725），它们占 DKK1 表型变异的 4.6%。此外，rs7069912 变异携带者的 DKK1 表达显著高于非携带者（P = 0.036）。在非洲裔家庭中，血清 DKK1 水平具有高度遗传性。DKK1 区域内的两个 SNP 占血清 DKK1 变异的近 5%。
