Cluster headache (CH) is a severe primary headache disorder with a genetic component, as indicated by family and twin studies. Diurnal and seasonal rhythmicity are key features of the disease and might be related to vitamin D, as low vitamin D levels have been observed in patients with cluster headache. In addition, the vitamin D receptor (VDR) occurs in brain areas and particularly in the hypothalamus. The aim of the present case–control study was to investigate the association of cluster headache susceptibility and clinical phenotypes with the VDR gene polymorphisms FokI, BsmI and TaqI in a Southeastern European Caucasian population. DNA was extracted from 131 unrelated CH patients and 282 non-headache controls and genotyped using real-time PCR (melting curve analysis). Linkage disequilibrium (LD) analysis confirmed that BsmI and TaqI, both located in the 3′UTR of the VDR gene, are in strong LD. Genotype and allele frequency distribution analysis of the VDR FokI, BsmI, and TaqI polymorphisms showed no statistically significant difference between cases and controls, whereas haplotype analysis indicated that the TAC haplotype might be associated with decreased cluster headache susceptibility. Intra-patient analysis according to diverse clinical phenotypes showed an association of the BsmI GG and TaqI TT genotypes with more frequent occurrence of CH attacks in this cohort. Therefore, a possible association was observed between VDR gene polymorphisms BsmI and TaqI or a linked locus and susceptibility for cluster headache development and altered clinical phenotypes in the Southeastern European Caucasian study population. Further large-scale replication studies are needed to validate these findings.

家庭和双胞胎研究表明，丛集性头痛 (CH) 是一种严重的原发性头痛疾病，具有遗传成分。昼夜节律性和季节性节律性是该疾病的关键特征，可能与维生素 D 相关，因为在丛集性头痛患者中观察到低维生素 D 水平。此外，维生素 D 受体 (VDR) 存在于大脑区域，尤其是下丘脑。本病例对照研究的目的是调查丛集性头痛易感性和临床表型与VDR基因多态性FokI、BsmI和TaqI的关联。在东南欧高加索人群中。从 131 名无关 CH 患者和 282 名非头痛对照中提取 DNA，并使用实时 PCR（熔解曲线分析）进行基因分型。连锁不平衡（LD）分析证实，BsmI和TaqI均位于VDR基因的 3'UTR ，处于强 LD。VDR FokI、BsmI和TaqI的基因型和等位基因频率分布分析多态性显示病例和对照之间没有统计学显着差异，而单倍型分析表明 TAC 单倍型可能与丛集性头痛易感性降低有关。根据不同临床表型的患者内分析显示BsmI GG 和TaqI TT 基因型与该队列中更频繁发生的 CH 发作有关。因此，观察到VDR基因多态性BsmI和TaqI之间可能存在关联或东南欧高加索研究人群中丛集性头痛发展和临床表型改变的相关位点和易感性。需要进一步的大规模复制研究来验证这些发现。