HCRTR2、ADH4 和 CLOCK 基因与丛集性头痛的遗传关联：一项基于中国人群的病例对照研究。
Genetic association of HCRTR2, ADH4 and CLOCK genes with cluster headache: a Chinese population-based case-control study.
机构信息
Department of Neurology, Chinese People's Liberation Army General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
The third department of Neurology, Affiliated Xingtai People's Hospital of Hebei Medical University, Xingtai, Hebei Province, 054000, China.
出版信息
J Headache Pain. 2018 Jan 9;19(1):1. doi: 10.1186/s10194-017-0831-1.
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.
背景
丛集性头痛（CH）是一种罕见的原发性头痛障碍，目前被认为是一种遗传易感性，在 CH 易感性中起作用。大量的遗传关联研究证实，HCRTR2（Hypocretin Receptor 2）SNP rs2653349、ADH4（Alcohol Dehydrogenase 4）SNP rs1126671 和 rs1800759 多态性与 CH 有关。此外，由于编码转录因子 CLOCK（Circadian Locomotor Output Cycles Kaput）基因，它成为 CH 的研究热点，该转录因子是人类昼夜节律的基本驱动力。本研究旨在评估 CH 与 HCRTR2、ADH4 和 CLOCK 基因在中国 CH 病例对照样本中的相关性。
方法
我们使用Sequenom MALDI-TOF Mass Spectrometry iPLEX 平台对 HCRTR2、ADH4 和 CLOCK 基因中的 9 个单核苷酸多态性（SNP）进行基因分型，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。比较病例组和对照组之间基因型和单倍型的频率和分布，以确定与 CH 的关联。进一步通过多元逻辑回归分析 SNP 对 CH 的影响。
结果
HCRTR2 SNP rs3800539GA 基因型在病例组中的频率明显高于对照组（48.2% vs.37.0%）。GA 基因型与 CH 风险增加相关（OR=1.483，95%CI：0.564-3.387，p=0.038），但经 Bonferroni 校正后，该关联失去统计学意义。HCRTR2SNP 的单体型分析表明，在 8 个单体型中，只有 H1-GTGGGG 与 CH 风险降低相关（44.7% vs.53.1%，OR=0.689，95%CI=0.491-0.966，p=0.030）。本研究未发现 ADH4、CLOCK SNP 与 CH 之间存在显著关联。
结论
本研究未发现 HCRTR2、ADH4、CLOCK 基因多态性与 CH 之间存在显著关联，但单体型分析表明 H1-GTGGGG 与 CH 风险降低相关。
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