Summary: 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.
Purpose: 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.
Methods: 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.
Results: 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).
Conclusion: 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.