Hypertension is a major risk factor for cardiovascular diseases, leading to serious health complications. Genetic polymorphisms in the COX-2 gene, especially the rs689466 variant, are associated with increased cardiovascular risk, but its link to hypertension in the Indonesian population remains limited. This study investigates the relationship between COX-2 rs689466 polymorphism and hypertension in Indonesia, using a cross-sectional design with 200 samples (100 hypertensive patients and 100 healthy individuals). DNA was isolated from whole blood using the salting-out method, and the COX-2 rs689466 polymorphism was analyzed by PCR-RFLP. Statistical analysis was performed using the Chi-square and Mann-Whitney tests. The results showed a significant association between the COX-2 rs689466 polymorphism and hypertension (p<0.001), with the AA genotype carrying a higher risk (p<0.001, OR=8.609) compared to individuals with the GG or AG genotypes. Smoking exacerbated this association, with smokers being more likely to carry the AA genotype and have an increased risk of hypertension (p<0.001, OR=6.091). This study highlights the role of COX-2 rs689466, particularly the AA genotype, in increasing hypertension risk in Indonesia, with smoking further worsening vascular inflammation and resistance, contributing to hypertension development.Keywords - Cyclooxygenase-2 (COX-2), Hypertension, Polymorphism, Smoking, Rs689466.
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