Hong Seok Ho, Wang Kyu-Chang, Kim Seung-Ki, Cho Byung-Kyu, Park Myoung Hee
Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.
J Korean Neurosurg Soc. 2009 Dec;46(6):558-63. doi: 10.3340/jkns.2009.46.6.558. Epub 2009 Dec 31.
Moyamoya disease (MMD) is an uncommon cerebrovascular disorder, characterized by progressive occlusion at the terminal portion of the internal carotid artery. Incidence of the disease is high in East Asia and familial MMD accounts for about 15% of the disease. Although the pathogenesis is unknown, association of HLA class I or II alleles with MMD has been reported with conflicting results. We investigated whether there is a difference in HLA class II association between familial and non-familial forms of the disease.
A total of 70 Korean children with MMD, including 16 familial cases (10 probands), and 207 healthy controls were studied. Among familial cases, only 10 probands were used for the HLA frequency analysis. High resolution HLA-DRB1 and DQB1 genotyping was performed using polymerase chain reaction (PCR)-sequence specific oligonucleotide hybridization and PCR-single strand conformation polymorphism methods.
The phenotype frequencies of HLA-DRB1()1302 (70.0%) and DQB1()0609 (40.0%) were significantly increased in familial MMD compared to both controls [vs. 15.5%, corrected p (p(c)) = 0.008, odds ratio (OR) = 12.76; vs. 4.3%, p(c) = 0.02, OR = 14.67] and non-familial MMD patients (vs. 14.8%, p(c) = 0.02, OR = 13.42; vs. 1.9%, p(c) = 0.02, OR = 35.33). The frequencies of DRB1 and DQB1 alleles in non-familial MMD patients were not significantly different from those in controls.
Our findings suggest that the genetic polymorphism of HLA class II genes or other closely linked disease relevant gene(s) could be a genetic predisposing factor for familial MMD.
烟雾病（MMD）是一种罕见的脑血管疾病，其特征为颈内动脉末端进行性闭塞。该病在东亚地区发病率较高，家族性烟雾病约占该病的15%。尽管其发病机制尚不清楚，但已有报道称HLA I类或II类等位基因与烟雾病有关，结果相互矛盾。我们调查了家族性和非家族性烟雾病在HLA II类关联方面是否存在差异。
共研究了70例韩国烟雾病患儿，其中包括16例家族性病例（10例先证者）和207例健康对照。在家族性病例中，仅10例先证者用于HLA频率分析。采用聚合酶链反应（PCR）-序列特异性寡核苷酸杂交和PCR-单链构象多态性方法进行高分辨率HLA-DRB1和DQB1基因分型。
与对照组[分别为15.5%，校正p值（p(c)）=0.008，优势比（OR）=12.76；4.3%，p(c)=0.02，OR=14.67]和非家族性烟雾病患者相比[分别为14.8%，p(c)=0.02，OR=13.42；1.9%，p(c)=0.02，OR=35.33]，家族性烟雾病中HLA-DRB1（）1302（70.0%）和DQB1（）0609（40.0%）的表型频率显著升高。非家族性烟雾病患者中DRB1和DQB1等位基因频率与对照组无显著差异。
我们的研究结果表明，HLA II类基因或其他紧密连锁的疾病相关基因的遗传多态性可能是家族性烟雾病的遗传易感因素。
