Genetic insights into migraine pathophysiology: COX-2 1195 A>G (rs689466) and COX-2 765 G>C (rs20417) polymorphisms and their clinical implications.

OBJECTIVES

This study aimed to investigate the association of COX-2 gene polymorphisms with key clinical features of migraine, including headache onset, duration, severity, and associated symptoms such as depression and nausea.

METHODS

A total of 100 migraineurs were enrolled. DNA was extracted from blood samples and analyzed for COX-2 gene polymorphisms using PCR-RFLP.

RESULTS

Patients with a family history of migraine experienced an earlier onset of headaches (p = 0.005), particularly those with migraine without aura and a positive family history (p < 0.001). Women with hereditary migraine also showed earlier headache onset (p = 0.008). Within the migraine with aura subgroup, preliminary analysis indicated that carriers of the G+ (GG+AG) genotype had significantly longer headache durations than those with the AA genotype (p = 0.016). A strong correlation between pain severity and nausea was observed (p < 0.0001). Machine learning regression analysis revealed that the COX-2 1195 A > G polymorphism showed a comparatively higher, though still marginal, predictive contribution to migraine severity than other predictors; however, the overall predictive signal remained modest. Given the limited size of certain patient subgroups, these genotype-based associations should be interpreted with caution.

CONCLUSIONS

Our findings provide preliminary evidence that COX-2 gene polymorphisms, particularly the 1195 A > G variant, may be associated with migraine clinical features, such as onset and severity. However, given limited subgroup sizes, these associations should be interpreted with caution. Further investigation in larger, independent cohorts is warranted to validate these results and clarify the role of the COX-2 pathway in migraine pathophysiology.