ZMIZ1区域单核苷酸多态性rs11593576与汉族人白癜风表型相关性研究

发布时间：2018-09-18 08:08

【摘要】：研究背景:白癜风(vitiligo)是一种常见的、累及皮肤和毛囊的色素脱失性皮肤病,可发生于全身任何部位,男女均可发病,全世界发病率约为~1%。各地区的发病率存在明显差异,中国汉族人的发病率约为0.19%。迄今为止,白癜风的发病机制尚不清楚,常见的发病学说有自身免疫学说、遗传学说、神经起源学说和黑素细胞自身破坏学说。但每种学说只能解释疾病的一小部分。临床和流行病学调查显示白癜风可能是一种多基因遗传性疾病。连锁和关联研究发现了白癜风多个遗传易感基因,但只有几个位点,例如NLRP1 (编码NLR家族,又叫NALP1)和HLA等位基因在多项研究中被重复。最近,我们团队在中国汉族人白癜风易感基因全基因组关联分析中发现,ZMIZ1(SNP rs11593576)与汉族人白癜风有关联。目的:研究ZMIZ1(SNP rs11593576)与汉族人白癜风某些临床表型之间的关系,为阐述白癜风的发病机制打下基础。方法:采用统一设计的白癜风遗传流行病学调查表和正常对照调查表,由经过专门培训的流行病学调查员以问卷调查的形式,收集白癜风病例6585例,对照8178例。所有研究对象的ZMIZ1区域SNP rs11593576基因分型资料均来源于本研究小组利用Illumina 610芯片对汉族人白癜风进行全基因组关联分析的基因分型数据。用Epi Info 6.0软件建立数据库,采用SPSS13.0软件进行统计学分析。结果:1.rs11593576等位基因和基因型分布频率在病例组和对照组之间均有显著性差异(P值分别为3.93×10~(-8)和4.81×10~(-7))。将病例按照临床表型分组后分别与对照组比较,等位基因和基因型的分布频率在各表型组与对照组间的差异仍具有统计学意义(等位基因频率在泛发型和对照组、肢端型和对照组之间差异无统计学意义,基因型频率在泛发型与对照组之间无意义)。2. SNP rs11593576等位基因和基因型频率在病例各临床表型间均无意义(P0.05)。结论:SNP rs11593576与汉族人白癜风(泛发型除外)的易感性相关,但与白癜风患者的家族史、发病年龄、有无伴发疾病、皮损类型可能无显著相关性。
[Abstract]:BACKGROUND: Vitiligo is a common depigmented dermatosis involving skin and hair follicles. It can occur anywhere in the body. The incidence of vitiligo in men and women is about 1% worldwide. The incidence of vitiligo varies greatly from region to region. The incidence of vitiligo in Chinese Han people is about 0.19%. It's not clear. Common pathogenesis theories include autoimmunity, genetics, neurogenesis, and melanocyte self-destruction. But each theory accounts for only a small fraction of the disease. Clinical and epidemiological investigations suggest that vitiligo may be a polygenic inherited disease. Linkage and association studies have identified multiple legacies of vitiligo. We recently found that ZMIZ1 (SNP rs11593576) was associated with vitiligo in Chinese Han population by genome-wide association analysis. Objective: To study the association between ZMIZ1 (SNP rs11593576) and vitiligo in Chinese Han population. 576) The relationship between vitiligo and some clinical phenotypes in Han nationality lays a foundation for explaining the pathogenesis of vitiligo.
Methods: A uniformly designed genetic epidemiological questionnaire and a normal control questionnaire were used to collect 6585 cases of vitiligo and 8178 cases of control by specially trained epidemiologists. The genotyping data of SNP rs11593576 in ZMIZ1 region of all subjects were obtained from the study group. Genome-wide association analysis of vitiligo was performed by Illumina 610 microarray. Epi Info 6.0 software was used to establish a database and SPSS 13.0 software was used for statistical analysis. Results: 1. The allele and genotype distribution frequencies of rs11593576 were significantly different between the case group and the control group (P values were 3.93 *10 ~ respectively). (8) and 4.81 * 10 ~ (- 7). After grouping the patients according to the clinical phenotype, the distribution frequencies of alleles and genotypes were still significantly different between the phenotype group and the control group (allele frequencies were not significantly different between the generalized hairstyle and the control group, acrotype and the control group, genotype frequencies were significantly different between the phenotype group and the control group). The allele and genotype frequencies of SNP rs11593576 were not significant among the clinical phenotypes (P 0.05).
Conclusion: SNP rs11593576 is associated with susceptibility to vitiligo (except for generalized vitiligo) in Han nationality, but not with family history, age of onset, concomitant disease and type of skin lesion.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R758.41

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