A haplotype derived from the common variants at the -1997G/T and Sp1 binding site of the COL1A1 gene influences risk of postmenopausal osteoporosis in India

Rheumatol Int (2013) 33:501506 DOI 10.1007/s00296-011-2192-4

SHORT COMMUNICATION

A haplotype derived from the common variants at the 21997G/T and Sp1 binding site of the COL1A1 gene inuences riskof postmenopausal osteoporosis in India

Monica Singh Puneetpal Singh Surinder Singh

Pawan Kumar Juneja Taranpal Kaur

Received: 20 May 2011 / Accepted: 22 October 2011 / Published online: 6 November 2011 Springer-Verlag 2011

Abstract The aim of the present study was to investigate the association between Collagen 1 alpha 1 (COL1A1) polymorphism and osteoporosis in DEXA veried 349 (145 osteoporotic, 87 osteopenic and 117 normal) postmenopausal women of India, who were not taking hormone replacement therapy. Two single-nucleotide polymorphisms (SNPs), that is, -1997G/T (rs1107946) and ?1245G/T (rs1800012, Sp1) of the COL1A1 gene, were analyzed. Minor allele frequencies of rs1107946 and rs1800012 were 0.15 and 0.20 in osteoporotic women, 0.18 and 0.18 in osteopenic and 0.20 and 0.17 in women having normal bone mass. An allele dose effect with BMD of lumbar spine has been exhibited by major allele G of rs1107946 (GG: 0.86 g/cm2, GT: 0.91 g/cm2 and TT: 0.93 g/cm2) and minor allele T of rs1800012 (GG:0.91 g/cm2, GT: 0.87 g/cm2 and TT: 0.81 g/cm2). Disease association analysis revealed a haplotype GT that confers approximately threefold higher risk of osteoporosis in the carriers (OR 3.12, 95% CI 1.248.88, P = 0.008) after adjusting the confounding effect of age, BMI and years since menopause. These results suggest that GT haplotype of COL1A1 gene is associated with a higher risk of postmenopausal osteoporosis in Northwest Indian women.

Keywords COL1A1 gene rs1107946 rs1800012

Haplotypes BMD Postmenopausal women India

Introduction

Osteoporosis, a skeletal disease characterized by reduced bone mineral density (BMD) and increased fracture risk

has a strong genetic inuence [1]. A large number of genes have been reported to be associated with reduced BMD and osteoporosis risk [2, 3], but the data from different studies have been conicting. Type I collagen is the most abundant protein constituent of the bone matrix and, therefore, a strong and plausible candidate gene for the regulation of BMD. Several studies have investigated the possible association of allelic variants within collagen 1 alpha 1 (COL1A1) gene with postmenopausal osteoporosis [412]. Lately, a meta-analysis of 32 studies on the 50 ank of

COL1A1 gene has...