Multi-Drug Resistance 1 Gene C3435T Polymorphism in Migraine Patients: A Case-Control Study

Background: Migraine is a complex neurovascular disorder with a substantial genetic component. The multidrug resistance 1 (MDR1/ABCB1) gene encodes P-glycoprotein, a key efflux transporter at the blood–brain barrier that regulates the distribution of neuroactive compounds. The functional C3435T polymorphism (rs1045642) has been suggested to influence transporter activity; however, its role in migraine susceptibility remains inconclusive. Methods: This case–control study included 100 patients with migraine diagnosed according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) and 100 age- and sex-matched healthy controls. Genotyping of the MDR1 C3435T polymorphism was performed using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. Genotype and allele distributions were analyzed under different genetic models. Multivariate logistic regression analysis was conducted to adjust for potential confounders, including age, sex, body mass index, and biochemical parameters. Bonferroni and false discovery rate (FDR) corrections were applied to account for multiple comparisons. Results: Genotype distributions were consistent with the Hardy–Weinberg equilibrium in both groups (p > 0.05). The overall genotype distribution did not differ significantly between migraine patients and controls (χ2 = 4.54, p = 0.103). However, the TT genotype was significantly more frequent in the migraine group (40.0% vs. 30.0%; odds ratio (OR) = 2.38, 95% confidence interval (CI): 1.06–5.34, p = 0.035). The dominant model (CT+TT vs. CC) showed borderline significance (p = 0.052). The T allele frequency was significantly higher in patients compared to controls (63.0% vs. 52.5%; OR = 1.54, 95% CI: 1.03–2.30, χ2 = 4.519, p = 0.034). However, these associations did not remain statistically significant after Bonferroni and FDR corrections. Multivariate logistic regression analysis yielded comparable results, indicating that the observed associations were not independent of potential confounders. Conclusion: The MDR1 C3435T polymorphism may be modestly associated with migraine susceptibility in a genotype-specific manner; however, the lack of significance after correction for multiple testing suggests that this variant is unlikely to represent a strong or independent genetic predictor. Further large-scale, multi-center studies incorporating haplotype analyses and environmental factors are warranted.