<i>COX‑2</i> rs20417 polymorphism and susceptibility to type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a multifactorial disease influenced by environmental and genetic factors. The present case-control study aimed to evaluate the association between three cyclooxygenase-2 (<i>COX-2</i>) gene polymorphisms (rs689466, rs20417 and rs2066826) and the susceptibility to T2DM in the Jordanian population. A total of 202 participants were enrolled, comprising 101 patients with T2DM and 101 healthy controls matched by sex and age (±5 years). Genotyping was performed using PCR-restriction fragment length polymorphism, and clinical and biochemical parameters were assessed. The rs20417 polymorphism showed a significant association with T2DM. In multivariate logistic regression analysis adjusted for age, sex, body mass index, hypertension and triglyceride levels, individuals carrying the CG genotype were more likely to develop T2DM [odds ratio (OR)=5.09; 95% CI: 1.18-21.96; P=0.0290], as did those with the CC genotype (OR=5.39; 95% CI: 1.34-21.72; P=0.0178), compared with those with the GG genotype. No significant associations were observed for rs689466 or rs2066826. Haplotype analysis identified the T-C-C haplotype (rs689466-rs20417-rs2066826) as a risk haplotype associated with increased susceptibility to T2DM (OR=1.52; 95% CI: 1.01-2.30; P=0.046). These findings suggest that the <i>COX-2</i> rs20417 polymorphism is independently associated with T2DM risk in Jordanians, supporting a role for COX-2-mediated inflammatory pathways in the pathogenesis of diabetes.