Asuni Carlo, Stochino Maria Erminia, Cherchi Alessandra, Manchia Mirko, Congiu Donatella, Manconi Francesca, Squassina Alessio, Piccardi Maria Paola, Del Zompo Maria
Headache Centre Franco Tocco, Section of Clinical Pharmacology, Dept. of Neurosciences BB Brodie, University of Cagliari, PO San Giovanni di Dio, Via Ospedale 46, 09124 Cagliari, Italy.
J Neurol. 2009 Feb;256(2):194-7. doi: 10.1007/s00415-009-0961-8. Epub 2009 Mar 1.
To assess the possibility of an association between TNF gene polymorphisms and migraine without aura, a case-control study was performed in a Sardinian sample. Migraine without aura is a complex genetic disease in which susceptibility and environmental factors contribute towards its development. Several studies suggest that tumour necrosis factors (TNF) (TNF-alpha and lymphotoxin-alpha or TNF-ss) may be involved in the pathophysiology of migraine. The TNF-alpha and TNF-ss genes are located on chromosome 6p21.3 in the human leukocyte antigene (HLA) class III region. We evaluated 299 patients affected by migraine without aura (I.H.S. criteria 2004) and 278 migraine-free controls. The polymorphisms G308A of the TNF- alpha gene, and G252A of TNF-beta gene were determined by NcoI restriction fragment length polymorphism analysis. We found a statistically significant difference in allele (p = 0.018; OR = 1.46 95 % CI: 1.066 to 2.023) and genotype (trend chi2 = 5.46, df = 1, p = 0.019) frequencies of TNF-beta gene, between cases and controls. Allele and genotype frequencies of TNF-alpha polymorphism did not differ significantly between the two groups. These data suggest that subjects with the TNFB2 allele have a low risk of developing migraine without aura and/or that the polymorphism of the TNF-beta gene is in linkage disequilibrium with other migraine responsible genes in the HLA region.
为评估肿瘤坏死因子（TNF）基因多态性与无先兆偏头痛之间存在关联的可能性，在撒丁岛人群样本中开展了一项病例对照研究。无先兆偏头痛是一种复杂的遗传性疾病，其易感性和环境因素均对疾病发展有影响。多项研究表明，肿瘤坏死因子（TNF）（TNF-α和淋巴毒素-α或TNF-β）可能参与偏头痛的病理生理过程。TNF-α和TNF-β基因位于人类白细胞抗原（HLA）Ⅲ类区域的6号染色体p21.3上。我们评估了299例无先兆偏头痛患者（按照2004年国际头痛协会标准）和278例无偏头痛的对照者。通过NcoI限制性片段长度多态性分析确定了TNF-α基因的G308A多态性和TNF-β基因的G252A多态性。我们发现，病例组和对照组之间，TNF-β基因的等位基因频率（p = 0.018；OR = 1.46，95%CI：1.066至2.023）和基因型频率（趋势卡方= 5.46，自由度= 1，p = 0.019）存在统计学显著差异。两组之间TNF-α多态性的等位基因和基因型频率无显著差异。这些数据表明，携带TNFB2等位基因的个体发生无先兆偏头痛的风险较低，和/或TNF-β基因的多态性与HLA区域中其他与偏头痛相关的基因处于连锁不平衡状态。
