Abstract
BackgroundCluster headache (CH), a rare primary headache disorder, is currently thought to be a genetic susceptibility which play a role in CH susceptibility. A large numbers of genetic association studies have confirmed that the HCRTR2 (Hypocretin Receptor 2) SNP rs2653349, and the ADH4 (Alcohol Dehydrogenase 4) SNP rs1126671 and rs1800759 polymorphisms are linked to CH. In addition, the CLOCK (Circadian Locomotor Output Cycles Kaput) gene is becoming a research hotspot for CH due to encoding a transcription factor that serves as a basic driving force for circadian rhythm in humans. The purpose of this study was to evaluate the association between CH and the HCRTR2, ADH4 and CLOCK genes in a Chinese CH case–control sample.MethodsWe genotyped polymorphisms of nine single nucleotide polymorphisms (SNPs) in the HCRTR2, ADH4 and CLOCK genes to perform an association study on a Chinese Han CH case-control sample (112 patients and 192 controls),using Sequenom MALDI-TOF mass spectrometry iPLEX platform. The frequencies and distributions of genotypes and haplotypes were statistically compared between the case and control groups to identify associations with CH. The effects of SNPs on CH were further investigated by multiple logistic regression.ResultsThe frequency of the HCRTR2 SNP rs3800539 GA genotype was significantly higher in cases than in controls (48.2% vs.37.0%). The GA genotypes was associated with a higher CH risk (OR = 1.483, 95% CI: 0.564-3.387, p = 0.038), however, after Bonferroni correction, the association lost statistical significance. Haplotype analysis of the HCRTR2 SNPs showed that among eight haplotypes, only H1-GTGGGG was linked to a reduced CH risk (44.7% vs. 53.1%, OR = 0.689, 95% CI =0.491~0.966, p = 0.030). No significant association of ADH4, CLOCK SNPs with CH was statistically detected in the present study.ConclusionsAssociation between HCRTR2, ADH4,CLOCK gene polymorphisms and CH was not significant in the present study, however, haplotype analysis indicated H1-GTGGGG was linked to a reduced CH risk.
Highlights
Cluster headache (CH), a rare primary headache disorder, is currently thought to be a genetic susceptibility which play a role in CH susceptibility
The purpose of this study was to evaluate the association between CH and the HCRTR2, ADH4(rs1126671、rs1800759) and Circadian Locomotor Output Cycles Kaput (CLOCK) genes, estimating the frequency of different gene haplotypes in a Chinese case–control cohort population
Genotype and allele frequency of the polymorphisms between the cases and controls genotype and allelic analysis All the genes showed the polymorphisms of Single nucleotide polymorphisms (SNPs) except for rs1126671 that was excluded from the statistical analysis
Summary
Cluster headache (CH), a rare primary headache disorder, is currently thought to be a genetic susceptibility which play a role in CH susceptibility. The purpose of this study was to evaluate the association between CH and the HCRTR2, ADH4 and CLOCK genes in a Chinese CH case–control sample. Cluster headache (CH) is a relatively rare, severe type of primary trigeminal autonomic cephalalgia [1]. It has clinically unique features of excruciating unilateral periorbital pain with recurrent short-lasting attacks (15 to 180 min), accompanied by cranial autonomic symptoms, such as nasal congestion, runny nose (rhinorrhea), tears and eye congestion. CH is believed to be a genetic susceptibility disease, but at present, the type and the number of genes involved are still unclear
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