Molecular Genetics Laboratory, Department of Human Genetics, Punjabi University, Patiala, Punjab, India.
Arch Osteoporos. 2013;8:147. doi: 10.1007/s11657-013-0147-y. Epub 2013 Aug 22.
The influence of VDR gene for the risk of osteoporosis has remained inconclusive. VDR gene polymorphism in relation to BMD in postmenopausal women of Northwest India revealed a susceptibility haplotype AGT. Possession of this haplotype exacerbates the risk of osteoporosis by 2.8 times, which manifests in recessive mode of inheritance.
The purpose of this study is to understand the influence of coordinated effect of various single nucleotide polymorphisms (SNPs) within vitamin D receptor (VDR) gene for the risk of osteoporosis, which has remained undefined so far.
Four pertinent SNPs of VDR gene, i.e., rs2228570, rs1544410, rs17879735, and rs731236 were examined with polymerase chain reaction-restriction fragment length polymorphism in dual energy X-ray absorptiometry verified 188 osteoporotics, 115 osteopenics, and 147 normal postmenopausal women of Northwest India.
Minor allele 'T' of rs2228570 showed significant influence for the risk of osteoporosis (OR 1.60, 95%CI 1.16-2.20, P=0.004) and also in dominant (OR 2.32, 95%CI 1.47-3.64, P=0.0006) and additive model (OR 2.41, 95%CI 1.49-3.87, P=0.0006) after Bonferroni correction. Minor allele (T) of rs2228570 showed an allele dose effect with BMD of L1-L4 (P=0.009) and FN (P=0.036). Disease association analysis exposed a susceptibility haplotype AGT which influences the risk of osteopenia (OR 2.04, 95%CI 1.03-4.08, P=0.036) and osteoporosis (OR 2.90, 95%CI 1.61-5.38, P=0.00005) after adjusting the effects of age, BMI and years since menopause. This haplotype is significantly associated with BMDs at lumbar spine (P=0.0001) and femoral neck (P=0.016).
In-depth analysis of this haplotype with other methods of Wald statistics and Akaike information criterion confirmed that carriers of each unit of this haplotype AGT increases the risk of osteoporosis by a factor of 2.80±0.34 (β±SE) which manifests (P=0.1 × 10⁻⁶) in its recessive mode of inheritance.
维生素 D 受体（VDR）基因对骨质疏松症风险的影响仍存在争议。本研究旨在探讨 VDR 基因内多个单核苷酸多态性（SNP）的协同效应对骨质疏松症风险的影响，该影响迄今尚未明确。VDR 基因的 4 个相关 SNP（rs2228570、rs1544410、rs17879735 和 rs731236）通过聚合酶链反应-限制性片段长度多态性在双能 X 线吸收法（DXA）验证的 188 例骨质疏松症患者、115 例骨量减少症患者和 147 例印度西北部正常绝经后妇女中进行了检测。
rs2228570 的次要等位基因“T”对骨质疏松症风险有显著影响（OR 1.60，95%CI 1.16-2.20，P=0.004），并且在显性（OR 2.32，95%CI 1.47-3.64，P=0.0006）和加性模型（OR 2.41，95%CI 1.49-3.87，P=0.0006）中也有显著影响，经 Bonferroni 校正后。rs2228570 的次要等位基因（T）与 L1-L4 的 BMD（P=0.009）和 FN（P=0.036）呈等位基因剂量效应。疾病关联分析揭示了一个易感单倍型 AGT，该单倍型增加了骨量减少症（OR 2.04，95%CI 1.03-4.08，P=0.036）和骨质疏松症（OR 2.90，95%CI 1.61-5.38，P=0.00005）的风险，同时还调整了年龄、BMI 和绝经后年限的影响。该单倍型与腰椎（P=0.0001）和股骨颈（P=0.016）的 BMD 显著相关。
深入分析该单倍型的 Wald 统计和 Akaike 信息准则等方法证实，携带该单倍型 AGT 的每个单位增加了 2.80±0.34（β±SE）的骨质疏松症风险（P=0.1×10⁻⁶），以隐性遗传方式表现。
