The polymorphism rs2651899 of the PR/SET domain 16 gene is significantly associated with increased risk for common migraine subtypes, including migraine without aura and migraine with aura, according to study results published in Headache.
The investigators of this study performed a systematic review and meta-analysis to examine the role of rs2651899 in patients with migraine headache.
The investigators searched relevant databases (PubMed, Embase, and Google Scholar) for genome-wide association studies on the PR/SET domain 16 rs2651899 polymorphism and migraine published up to November 2018. Six studies were included in this meta-analysis, in which 2853 cases of migraine were identified and 9319 participants were used as controls. To measure the strength of the association between the rs2651899 polymorphism and common migraine subtypes, the investigators pooled individual odds ratios (ORs) and 95% confidence intervals (CI) for each study. To explore the mode of inheritance of the polymorphism in migraine, the investigators applied the allele model (C vs T), dominant model (C/C + C/T vs T/T) and recessive model (C/C vs T/T + C/T).
The rs2651899 polymorphism was associated with significant migraine risk for the allele model (OR 1.257; 95% CI, 1.175-1.344), dominant model (OR 1.305; 95% CI, 1.178-1.447), and recessive model (OR 1.419; 95% CI, 1.261-1.596). In subgroup analyses, the rs2651899 polymorphism was further associated with increased risk of migraine without aura in the allele model (OR 1.308; 95% CI, 1.169-1.463), dominant model (OR 1.349; 95% CI, 1.135-1.602), and recessive model (OR 1.546; 95% CI, 1.265-1.889). The PR/SET domain 16 rs2651899 polymorphism was also associated with a significant risk for migraine with aura in the allele model (OR 1.230; 95% CI, 1.069-1.415) and the recessive model (OR 1.454; 95% CI, 1.151-1.835), but not in the dominant model (OR 1.204; 95% CI, 0.967-1.500).
Limitations to the study included lack of data regarding the effects of gender and environmental risk factors, pooled estimates were not adjusted for potential confounders, and other migraine subtypes such as vestibular and basilar migraine were not considered.
The investigators suggest that participants who carried the C allele of PR/SET domain 16 rs2651899, along with participants carrying the dominant model, have significantly increased risks for both migraine with aura and migraine without aura. Participants who carried the recessive model of PR/SET domain 16rs2651899, however, had a significantly higher risk of developing migraine without aura vs migraine with aura.
Lee HH, Chen CC, Ong JR, et al. Association of rs2651899 polymorphism in the positive regulatory domain 16 and common migraine subtypes: a meta-analysis [published online September 26, 2019]. Headache. doi: 10.1111/head.13670