González-Mercado A, Sánchez-López J Y, Regla-Nava J A, Gámez-Nava J I, González-López L, Duran-Gonzalez J, Celis A, Perea-Díaz F J, Salazar-Páramo M, Ibarra B
División de Genética, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Jalisco, México.
Genet Mol Res. 2013 Jul 30;12(3):2755-63. doi: 10.4238/2013.July.30.13.
We investigated associations between vitamin D receptor (VDR) gene polymorphisms, FokI T>C (rs2228570), BsmI G>A (rs1544410), ApaI G>T (rs7975232), and TaqI T>C (rs731236), with bone mineral density (BMD) in postmenopausal Mexican-Mestizo women. Three hundred and twenty postmenopausal women participated, who were classified according to World Health Organization criteria as non-osteoporotic (Non-OP; N = 88), osteopenic (Opn; N = 144), and osteoporotic (OP; N = 88). BMD measurements at the lumbar (L1-L4) spine and at the left and right femoral neck were obtained by dual-energy X-ray absorptiometry. Single nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction and TaqMan probes. Genotype and allelic frequencies of the 4 VDR SNPs were similar among the 3 groups. Polymorphic allele frequencies were as follows: FokI (C) 0.53, 0.49, 0.56; BsmI (A) 0.26, 0.22, 0.23; ApaI (T) 0.43, 0.39, 0.44; TaqI (C) 0.27, 0.22, 0.23 for the Non-OP, Opn, and OP groups, respectively. Although no associations were found between the SNPs and BMD, based on the putative function of the FokI SNP, we constructed, for the first time, the haplotype with the 4 VDR SNPs, and found that the CGGT haplotype differed between the Non- OP and OP groups (21.8 vs 31.8%, P < 0.05). The risk analysis for this haplotype was nearly significant under the dominant model (OR = 1.783, 95%CI = 0.98-3.25, P = 0.058). This result suggests a possible susceptibility effect of the C allele of the FokI SNP for the development of osteoporosis in postmenopausal Mexican-Mestizo women.
我们研究了维生素D受体（VDR）基因多态性，即FokI T>C（rs2228570）、BsmI G>A（rs1544410）、ApaI G>T（rs7975232）和TaqI T>C（rs731236），与绝经后墨西哥梅斯蒂索女性骨密度（BMD）之间的关联。320名绝经后女性参与了研究，她们根据世界卫生组织标准被分类为非骨质疏松症（Non-OP；N = 88）、骨质减少（Opn；N = 144）和骨质疏松症（OP；N = 88）。通过双能X线吸收法测量腰椎（L1-L4）和左右股骨颈的骨密度。使用实时聚合酶链反应和TaqMan探针进行单核苷酸多态性（SNP）基因分型。这4个VDR SNP的基因型和等位基因频率在3组之间相似。多态性等位基因频率如下：Non-OP组、Opn组和OP组的FokI（C）分别为0.53、0.49、0.56；BsmI（A）分别为0.26、0.22、0.23；ApaI（T）分别为0.43、0.39、0.44；TaqI（C）分别为0.27、0.22、0.23。尽管未发现SNP与骨密度之间存在关联，但基于FokI SNP的推定功能，我们首次构建了包含这4个VDR SNP的单倍型，并发现Non-OP组和OP组之间的CGGT单倍型存在差异（21.8%对31.8%，P < 0.05）。在显性模型下，该单倍型的风险分析接近显著（OR = 1.783，95%CI = 0.98 - 3.25，P = 0.058）。这一结果表明，FokI SNP的C等位基因可能对绝经后墨西哥梅斯蒂索女性骨质疏松症的发生具有易感性作用。
