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

Abstract

The aim of the present study was to investigate the association between Collagen 1 alpha 1 (COL1A1) polymorphism and osteoporosis in DEXA verified 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/cm(2), GT: 0.91 g/cm(2) and TT: 0.93 g/cm(2)) and minor allele T of rs1800012 (GG: 0.91 g/cm(2), GT: 0.87 g/cm(2) and TT: 0.81 g/cm(2)). Disease association analysis revealed a haplotype GT that confers approximately threefold higher risk of osteoporosis in the carriers (OR 3.12, 95% CI 1.24-8.88, 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.

Effects of Administration of Amlodipine and Lacidipine on Inflammation-Induced Bone Loss in the Ovariectomized Rat

“…Collagen production decreases by genetic mutations and in the absence of elastin production such as Marfan's syndrome, affecting bone development directly [76]. Polymorphism studies of Col1a1 showed that the risk of osteoporosis increases in women [91,92].…”

Association of collagen type I alpha 1 +1245G/T polymorphism and osteoporosis risk in post-menopausal women: a meta-analysis

“…No additional articles were selected based on the manual search. Finally, a total of five studies were included in this meta‐analysis . The characteristics of the five included studies are shown in Table .…”

“…found the association of +1245G/T and −1663indelT polymorphic loci of COLIA1 gene with the risk of osteoporotic fractures in women from the Volga‐Ural area, and deem that −1997*G/−1663*D/+1245*T haplotype and −1997*G*G/−1663*I*D/+1245*G*T genotype combination can serve as markers for the development of fracture. The association between the +1245G/T (rs1800012, Sp1) and ‐1997G/T (rs1107946) polymorphisms of COL1A1 and osteoporosis have been investigated, and the results indicate that COL1A1 polymorphisms result in osteoporosis in post‐menopausal women from northwest India . By contrast, polymerase chain reaction (PCR) and SSCP analysis show that the presence of the T allele in the genotype of COL1A1 gene has no correlation with BMD in women with osteoporosis .…”

COL1A1 gene -1997G/T polymorphism and risk of osteoporosis in postmenopausal women: a meta-analysis

“…An additional paper did not have a control group and was further excluded. Therefore, only four studies of the association between the COL1A1 gene -1997G/T polymorphism and osteoporosis risk were selected for this meta-analysis (Selezneva et al, 2008;Husted et al, 2009;Li et al, 2010;Singh et al, 2013). Two studies were conducted in Europe and two in Asia.…”