MHC区域HLA-DPB1基因和BTNL2基因与汉族人银屑病临床表型相关性研究

发布时间：2018-04-15 01:26

本文选题：HLA + 寻常型银屑病　；参考：《安徽医科大学》2017年硕士论文

【摘要】：研究背景银屑病是一种涉及多基因和多因素的慢性复杂性疾病,目前银屑病的确切发病机制尚不清楚,主要认为由遗传因素、免疫因素、皮肤屏障功能和环境因素等共同的相互作用引起。临床上以寻常型银屑病(psoriasis vulgaris,PV)最常见。全世界约1-3%人口受银屑病的影响。其中中国人口中银屑病的患病率约为0.123%。最新的研究通过对汉族人口9906例健康对照和8874例银屑病患者HLA区域的深度测序,发现了HLA-DPB1*05:01、BTNL2基因为银屑病新的易感基因。本实验在此基础上,通过进一步对9906例健康对照和8874例寻常型银屑病病例进行临床分型(性别、家族史、发病年龄、发病类型、地域)的分层分析,探讨HLA-DPB1*05:01、BTNL2基因型与寻常型银屑病临床表型的关联性。研究目的对寻常型银屑病进行临床表型分型,按照发病年龄(早发和晚发)、性别(男性和女性)、发病类型(点滴型和斑块型)、家族史(阳性和阴性)及地域(南方和北方)分为不同的临床表型,探讨HLA-DPB1*05:01、BTNL2基因多态性与中国汉族人寻常型银屑病临床表型之间的关系。实验方法本实验中的9906例健康对照者和9946例PV患者均来自前期全基因组外显子测序所使用的样本。本实验团队前期对MHC区域的深度测序得出HLA-DPB*05:01、BTNL2基因与寻常型银屑病有关,本实验根据性别、发病年龄、地域、家族史和皮损类型进行临床表型分层分析,通过PLINK 1.07和SPSS 20.0软件分析比较对照组和病例组间等位基因和基因型分布频率,得出P值、比值比(OR值)、95%置信区间(95%CI),分析HLA-BPB1*05:01、BTNL2病例组间与病例组和对照组间的等位基因的关联性时,以α=0.05为标准来判断统计结果是否有意义。结果 1 HLA-DPB1*05:01基因中基因分布频率在寻常型银屑病病例组中低于正常对照组的分布频率(35.9%VS 36.4%,p=1.72×10~(-1),OR=0.978,95%CI:0.947-1.01)。HLA-DPB1*05:01基因型与PV临床表型相关性分析表明,在PV病例组与对照组对比中,HLA-DPB1*05:01基因型表达与发病类型中的点滴型(p=3.914×10~(-2),OR=0.9335,95%CI:0.8744-0.9966)及北方地域(p=1.182×10~(-3),OR=0.9108,95%CI:0.8607-0.9637)间存在相关性;而在病例组间比较中,则仅与地域差异(p=1.36×10~(-4),OR=1.134,95%CI:1.063-1.209)存在明显相关性;未发现与其他临床表型有相关性。2 BTNL2基因中T等位基因分布频率在寻常型银屑病病例组中低于正常对照组的分布频率(5.8%VS 6.3%,p=4.72×10~(-3),OR=0.911,95%CI:0.854-0.972)。BTNL2基因型与PV临床表型相关性分析显示,BTNL2基因的表达,在PV病例组与对照组分析中,发现与男性(p=2.563×10~(-2),OR=0.8897,95%CI:0.8029-0.9859),早发型(p=9.399×10~(-3),OR=0.8856,95%CI:0.808-0.9707),点滴型(p=2.469×10~(-2),OR=0.8558,95%CI:0.7469-0.9805),及阳性家族史(p=1.51×10~(-4),OR=0.772,95%CI:0.6069-0.8551)存在相关性;并在病例组间,与家族史(p=1.768×10~(-3),OR=0.757,95%CI:0.6355-0.9018),发病年龄(p=3.818×10~(-2),OR=1.195,95%CI:1.01-1.414)存在明显关联性,未发现与其他临床表型有相关性。结论 HLA-DPB*05:01基因与地域差异(p=1.36×10~(-4),OR=1.134,95%CI:1.063-1.209)存在显著相关性;BTNL2基因与家族史(p=1.768×10~(-3),OR=0.757,95%CI:0.6355-0.9018)及发病年龄(p=3.818×10~(-2),OR=1.195,95%CI:1.01-1.414)存在显著关联性。
[Abstract]:Backgroundpsoriasis is a multi gene and multi factor complex and chronic diseases, the exact pathogenesis of psoriasis is not clear at present, mainly by genetic factors, immune factors, caused by the interaction of skin barrier function and environmental factors. In clinical psoriasis vulgaris (psoriasis vulgaris PV) is the most common. The world population is about 1-3% by the influence of psoriasis. The Chinese psoriatic the population prevalence rate is about the latest research by deep sequencing of 0.123%. of the Han population in 9906 healthy controls and 8874 patients with psoriasis HLA region, found HLA-DPB1*05:01, BTNL2 genes for psoriasis susceptibility genes. The new experimental basis further, through the clinical of 9906 healthy controls and 8874 patients with psoriasis vulgaris were divided into type (gender, family history, age of onset, disease type, region) layers Analysis of HLA-DPB1*05:01, correlation of BTNL2 genotype and clinical phenotypes of psoriasis vulgaris. The purpose of clinical phenotype of psoriasis vulgaris, according to age (early and late), gender (male and female), disease type (guttate and plaque type), family history (positive and negative) and the region (North and South) is divided into different clinical phenotype of HLA-DPB1*05:01, the relationship between the clinical phenotype of BTNL2 gene polymorphism and China psoriasis vulgaris in Chinese Han population. The experimental methods in this experiment, 9906 healthy controls and 9946 PV patients from the whole exome sequencing using the sample. The experiment team early deep sequencing of the MHC region that HLA-DPB*05:01, BTNL2 genes and psoriasis vulgaris, according to gender, age, region, family history and skin damage type phenotype points Layer analysis, comparing the frequency distribution of alleles and genotypes between cases and controls group analysis by PLINK 1.07 and SPSS 20 software, the P value, the odds ratio (OR value), 95% confidence interval (95%CI), HLA-BPB1*05:01 analysis, BTNL2 correlation between the case group and between case group and control group. Gene, a =0.05 as the standard to judge the statistical result is meaningful. The gene distribution of HLA-DPB1*05:01 gene in 1 frequency lower than the frequency distribution of the normal control group in the cases of psoriasis vulgaris group (35.9%VS 36.4%, p=1.72 * 10~ (-1) OR=, 0.978,95%CI:0.947-1.01).HLA-DPB1*05:01 genotype and clinical phenotype of PV correlation analysis showed that in the case of PV group compared with the control group, the expression of guttate type HLA-DPB1*05:01 genotype and disease type in (p=3.914 * 10~ (-2), OR=0.9335,95%CI:0.8744-0.9966) and the northern region (p=1.182 * 10~ (-3), OR=0.9108,95%C I:0.8607-0.9637) the correlation between the comparison groups; while in, only with regional differences (p=1.36 * 10~ (-4), OR=1.134,95%CI:1.063-1.209) was significantly associated; did not find the frequency distribution of frequencies of T and.2 in BTNL2 gene gene correlation in cases of psoriasis vulgaris were lower than the normal control group and other clinical the phenotype (5.8%VS 6.3%, p=4.72 * 10~ (-3), OR=0.911,95%CI:0.854-0.972).BTNL2 genotype and clinical phenotype of PV correlation analysis showed that the gene expression of BTNL2, PV in case group and control group analysis, and the male (p=2.563 * 10~ (-2), OR=0.8897,95%CI:0.8029-0.9859), early onset (p=9.399 * 10~ (-3) OR=0.8856,95%CI:0.808-0.9707, (p=2.469), guttate * 10~ (-2), OR=0.8558,95%CI:0.7469-0.9805), and positive family history (p=1.51 * 10~ (-4), OR=0.772,95%CI:0.6069-0.8551) and the correlation exists between the case group, With family history (p=1.768 * 10~ (-3), OR=0.757,95%CI:0.6355-0.9018), age (p=3.818 * 10~ (-2), OR=1.195,95%CI:1.01-1.414) has obvious relevance, found no correlation with other clinical phenotype. Conclusion HLA-DPB*05:01 gene and regional differences (p=1.36 * 10~ (-4), OR=1.134,95%CI:1.063-1.209) there was significant correlation between the BTNL2 gene and the family; history (p=1.768 * 10~ (-3), OR=0.757,95%CI:0.6355-0.9018) and age (p=3.818 * 10~ (-2), OR=1.195,95%CI:1.01-1.414) there was significant correlation.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R758.63

【相似文献】