背景:丛集性头痛(CH),一种罕见的原发性头痛疾病,目前被认为是在CH易感性中起作用的遗传易感性。大量的遗传关联研究已经证实HCRTR2(Hypocretin受体2)SNPrs2653349和ADH4(酒精脱氢酶4)SNPrs1126671和rs1800759多态性与CH相关。此外,CLOCK(昼夜节律输出周期Kaput)基因由于编码一种转录因子而成为CH的研究热点,该转录因子是人类昼夜节律的基本驱动力。这项研究的目的是评估中国CH病例对照样本中CH与HCRTR2,ADH4和CLOCK基因之间的关联。
方法:我们对HCRTR2,ADH4和CLOCK基因中的9个单核苷酸多态性(SNPs)进行基因分型,以对中国汉族CH病例对照样本(112例患者和192例对照)进行关联研究。使用SequenomMALDI-TOF质谱iPLEX平台。在病例组和对照组之间对基因型和单倍型的频率和分布进行了统计比较,以确定与CH的关联。进一步通过多元logistic回归分析SNP对CH的影响。
结果:HCRTR2SNPrs3800539GA基因型的频率在病例中明显高于对照组(48.2%vs.37.0%)。GA基因型与较高的CH风险相关(OR=1.483,95%CI:0.564-3.387,p=0.038),然而,Bonferroni校正后,该关联失去了统计学意义。HCRTR2SNP的单倍型分析显示,在8个单倍型中,只有H1-GTGGGG与降低的CH风险相关(44.7%vs.53.1%,OR=0.689,95%CI=0.491~0.966,p=0.030)。在本研究中,在统计学上没有检测到ADH4,CLOCKSNP与CH的显着关联。
结论:在本研究中,HCRTR2、ADH4、CLOCK基因多态性与CH之间的关联不显著。然而,单倍型分析表明H1-GTGGGG与降低的CH风险相关.
BACKGROUND: Cluster 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.
METHODS: We 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.
RESULTS: The 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.
CONCLUSIONS: Association 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.