Composite genotypes encoding the cholecystokininergic system and the folate cycle are significantly associated with migraine

Abstract

Multilocus analysis, specifically, analysis of combined genotype frequencies may be promising in studying migraine biomarkers. The aim of the study was to search for composite genetic biomarkers, which would predict individual predisposition to migraine, obtained on the basis of gene polymorphisms that have already shown a statistical significance in a single-locus associative analysis. Methods. 155 patients with migraine aging 41.7 ± 12.5 who had been followed up at the University Clinic of Headache, Moscow, were evaluated (104 patients with episodic migraine and 51 with chronic migraine). All patients were white and residents of the Moscow region. The control group included 365 unexamined individuals (population control). Identification of The 22 genes under study (total, 31 SNPs) were identified by PCR, PCR-RFLP, allele-specific PCR, and real-time PCR. Combined genotypes associated with migraine were identified using the APSampler v3.6 software for polygenic data analysis. Results. Eight combined genotypes were identified with a highly significant association with migraine (OR>0.02) with the MAOA gene as the major one. Conclusion. Our data on migraine-associated combined genotypes indicate a significant role in the migraine pathogenesis of two biochemical systems, i) the cholecystokininergic system that regulates the release and reuptake of dopamine, and ii) the folate cycle, where homocysteine is metabolized to methionine. The results obtained in this study suggest a protective role of the VNT: R4 allele of the MAOA gene.