Independent and Interactive Effects of Sex and CYP2C9 Variant rs4918758 on Ischemic Stroke Risk in Taiwan Biobank

PURPOSE: Stroke is a complex health condition caused by multiple risk factors. We investigated whether the Cytochrome P450 2C9 (CYP2C9) rs4918758 polymorphism and sex were independently and interactively associated with ischemic stroke risk among Taiwan Biobank (TWB) participants. MATERIAL AND METHODS: We analyzed TWB data pertaining to 9197 female and 8625 male individuals. Data collected between 2008 and 2015 were linked to medical records in the National Health Insurance Database (NHIRD). Based on multiple logistic regression analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for ischemic stroke. RESULTS: We found that 441 women and 468 men had ischemic stroke. There were no differences in the risk of ischemic stroke between individuals with the TC/CC genotype and those with the TT genotype [OR (95% CI) = 1.04 (0.90–1.21)]. When compared to women, men had an OR of 1.03 (95% CI = 0.87–1.22) for ischemic stroke. Based on further analysis, sex was found to interact with polymorphism rs4918758 (p for interaction = 0.0019). After categorizing by sex, men with TC/CC genotype showed significant ORs but not women [OR (95% CI) = 1.32 (1.07–16.33) vs 0.83 (0.68–1.00)]. Further stratification by genotype showed that in comparison with their female counterparts, men with the TT and TC/CC genotypes had ORs of 0.59 (95% CI = 0.44–0.80) and 1.36 (95% CI = 1.10–1.68), respectively. CONCLUSION: According to our study, the TT genotype of rs4918758 was associated with a reduced risk of ischemic stroke in Taiwanese men when compared to women, whereas the TC/CC genotype was associated with a greater risk.