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.

No abstract

The present study investigated genetic variation in the 3' flanking region of ApoA-I (PstI), the 3' untranslated region of ApoC-III (SstI) and intron 2 of ApoA-IV (XbaI) in 435 type 2 diabetes mellitus patients, divided according to the presence or absence of coronary heart disease (CHD). Uncommon allele frequencies (P2, S2, X2) were 17.5%, 32.5%, 16.2% and 29.5%, 17.9%, 13.8% in patients with and without CHD, respectively. Linkage disequilibrium (D' = 0.31-0.73, p<0.01) was observed in all diallelic pairs except XbaI/PstI and XbaI/SstI in patients having CHD. Haplotype analysis revealed that P1-S2-X1 is a susceptibility haplotype that increases the risk of CHD in diabetes (OR 2.85, CI 1.51-5.61), exacerbating risk (OR 3.57, CI 1.81-7.45) even after adjustment for confounders. The findings in the present study suggest that each unit of P1-S2-X1 in diabetes increases the risk of CHD by a factor of 1.37+/-0.307 (beta + SE), which is manifest in its multiplicative mode.

Biological revelations have gradually started clearing the complex relationships of bones with lipids. Studies have shown that lipid proWles are related to bone mass, bone fragility and fracture risk [1,2]. It has been observed that oxidized lipids inhibit mineralization of bone, induce osteoblastic diVerentiation in vascular cells, and hyperlipidemia reduces bone density in mice [3].To understand the genetic link between lipids and osteoporosis risk, apolipoprotein E gene (APOE) is a potential candidate because of its vital contribution to both lipid and vitamin K metabolism. APOE is located on the chromosome 19q13.2 and has three codominant alleles i.e. APOE2, APOE3 and APOE4. It serves as a ligand for receptor-mediated uptake of lipoprotein particles, which are the main carriers of vitamin K, and availability of vitamin K is an essential step for the carboxylation of glutamic acid residues of osteocalcin, an important bone protein. A study has shown that decrease in bone mineral density (BMD) in hemodialysis patients is correlated with hyperlipidemia, and the risk of fractures in such patients varies according to APOE genotypes [4]. Some preliminary Wndings suggest that APOE contributes to the variation in cholesterol increase with menopause [5], and APOE-E4-negative subjects respond better to hormone replacement therapy (HRT) for lowering lipid levels than APOE-E4-positive subjects [6]. However, in what way, genomic changes within APOE inXuence lipids for the risk of osteoporosis remains unclear.The impact of individual APOE SNP or allelic variant on lipid levels may vary if another nearby SNP is also participating or in linkage disequilibrium with another functional SNP. Studies comprising single SNP would have overlooked coordinated eVects of such SNPs. The present study explored the SNP-SNP interactions of four pertinent APOE SNPs (rs440446, rs769450, rs429358 and rs7412) as the genetic mediators of lipids in postmenopausal osteoporotic women of Punjab Province of Northwest India.Out of 366 randomly selected postmenopausal women who were not using HRT and were aged between 45 and 70 (Mean age 53.2 § 9.2), 154 osteoporotic women (71-lumbar spine and 83-femoral neck cases) were enrolled after veriWcation of the fractures from original radiographs and validation by DEXA (dual energy X-ray absorptiometry) unless they met the exclusion criteria: hyperlipidemia, irregular cycles or premature ovarian failure (menopause < 38 years), women with surgical menopause, any systemic disease or receiving medications known to inXuence calcium metabolism. DEXA veriWed population-based 83 postmenopausal women were enrolled as controls, according to a random-digit invitation from residents of the same geographic suburban and rural areas from Northwest India with three main exclusion criteria: hyperlipidemia, any fracture before or after menopause or any anti-osteoporotic treatment. Detailed information on age, medical history, years since menopause and gynecological history was obtained from these subjects. Height and weight ...

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.