Association of the GPX1 rs1050450 single nucleotide variant and identification of the novel variant rs771425412 in patients with primary osteoporosis from Baghdad, Iraq

Abstract

Introduction and aim. Osteoporosis is a multifactorial bone disorder driven by genetic and environmental factors, with oxidative stress implicated in its pathogenesis. Glutathione peroxidase 1 (GPX1), a key antioxidant enzyme, modulates bone homeostasis by regulating reactive oxygen species. To our knowledge, this is the first study to report the rs771425412 variant of the GPX1 gene in association with primary osteoporosis. This study investigated the association between the single nucleotide variant (rs1050450 C>T and rs771425412 C>A) and the risk of primary osteoporosis in Iraqi patients. Material and methods. A case-control study was conducted involving 105 patients with primary osteoporosis and 105 age-/sex-matched healthy controls recruited from Baghdad Hospital. Peripheral blood genomic DNA was genotyped by PCR and direct sequencing. Results. The rs1050450-T allele was significantly more frequent in patients than in controls (25.7% vs. 10.95%; OR=2.68, 95% CI: 1.58–4.55, p<0.001), with the CT genotype increasing the risk (dominant model: OR=3.77, 95% CI: 2.08–6.86). Similarly, the rs771425412-A allele was enriched in patients compared to controls (17.1% vs. 2.9%; OR=7.03, 95% CI: 2.93–16.92, p<0.001), and the CA genotype increased risk (OR=8.61, 95% CI: 3.47–21.3). Haplotype analysis revealed a protective C-C haplotype (OR=0.31, 95% CI: 0.19–0.51), while the T-A (OR=23.2, 95% CI: 3.09–174.3) and C-A (OR=3.15, 95% CI=1.12–8.8) haplotypes were associated with increased susceptibility. Conclusion. The CT genotype of rs1050450 and the CA genotype of rs771425412 in the GPX1 gene are significantly associated with an increased susceptibility to primary osteoporosis in the Iraqi population, likely through mechanisms involving impaired oxidative stress regulation.