HLA class I alleles are associated with clinic-based migraine and increased risks of chronic migraine and medication overuse

Abstract

Objective We aimed to evaluate associations of human leukocyte antigen variants with migraine or headache in hospital and population-based settings. Methods The case-control study population, aged 30–70, included 605 clinic-based migraine patients in a medical center and 8449 population-based participants in Taiwan Biobank (TWB). Clinic-based cases were ascertained by neurologists. Participants in Taiwan Biobank were interviewed by a structured questionnaire including headache and migraine history; among them, 2394 had headache or migraine history while 6055 were free of headache and served as controls. All subjects were genotyped by Axiom Genome-Wide Single Nucleotide Polymorphism Arrays and imputed for eight classical human leukocyte antigen genes. Human leukocyte antigen frequencies were compared between clinic-based and self-reported patients and controls. We utilized likelihood ratio tests to examine human leukocyte antigen-disease associations and logistic regressions to estimate the effect of human leukocyte antigen alleles on migraine. Results Human leukocyte antigen -B and C showed significant associations with clinic-based migraine ( q-value < 0.05). Human leukocyte antigen -B*39:01, human leukocyte antigen -B*51:01, human leukocyte antigen -B*58:01 and human leukocyte antigen -C*03:02 were significantly associated with migraine, with age and sex-adjusted odds ratios (95% CIs) of 1.80 (1.28–2.53), 1.50 (1.15–1.97), 1.36 (1.14–1.62) and 1.36 (1.14–1.62), correspondingly. Clinic-based migraineurs carrying human leukocyte antigen -B*58:01 or human leukocyte antigen -C*03:02 had 1.63 (1.11–2.39) -fold likelihood to have chronic migraine with medication-overuse headache compared to episodic migraine. However, no human leukocyte antigen genes were associated with self-reported headache or migraine in the community. Conclusions Human leukocyte antigen class I genetic variants are positively associated with risk of clinic-based migraine but not self-reported migraine or headache and may contribute to migraine chronification and medication overuse.