Are Methylenetetrahydrofolate Reductase (<i>MTHFR</i>) Gene Polymorphisms C677T and A1298C Associated with Higher Risk of Pediatric Migraine in Boys and Girls?

Abstract

Introduction: Women have been reported to have a higher risk for migraine. The pathogenesis of migraine is known to be related to genetic risk factors such as the presence of common polymorphisms C677T (rs1801133) and A1298C (rs1801131) in the MTHFR gene. The aim of the study was to examine the role of these two MTHFR polymorphisms as risk factors for pediatric migraine and examine the gender-specific differences. Methods: 56 patients (M = 26; F = 30) with migraine were randomly selected from Tartu University Hospital Children’s Clinic. 29 patients had migraine with aura (M = 13, F = 16) and 27 migraine without aura (M = 13, F = 14). The average age of the patients was 12.7 yrs (SD = 3.3). The control group consisted of 168 healthy people (M = 78, F = 90), ages 22 - 35 yrs (average 29.2 ± 3.4). Results: Among patients with aura, girls had higher frequency of A1298C and C677T mutations than boys, but not with statistical significance (minor allele frequency 0.406 and 0.231, p = 0.16; minor allele frequency 0.313 and 0.269, p = 0.72; respectively). In the migraine without aura group, girls had higher frequency in C677T (minor allele frequency 0.357 vs 0.231, p = 0.31) than boys. Comparing the migraine group with controls, higher frequencies of minor allele of A1298C and C677T in female patients were found (p = 0.63 and p = 0.32 respectively). In contrast, the C677T minor allele occurred in male controls with higher frequency (p = 0.34). Conclusion: Our results indicate a possible contribution of common MTHFR gene polymorphisms to migraine risk in children. 91% of children with migraine carried the variant alleles. Among girls, MTHFR polymorphisms occurred more frequently than among boys, but these differences were not statistically significant. We found that girls with migraine (with and without aura) showed an increased prevalence of C677T polymorphisms.