【作者】 唐先发；

【导师】 杜卫东； 张学军；

【作者基本信息】 安徽医科大学 ， 皮肤病与性病学， 2009， 硕士

【摘要】 研究背景:银屑病（Psoriasis,OMIM#177900）是一种常见的慢性复发性炎症性皮肤病,遗传因素与环境因素在疾病的发生过程中起重要作用。寻常型银屑病（Psoriasis Vulgaris,PV）是最常见的临床类型。本课题组通过全基因组关联分析（Genome-wide Association Study,GWAS）研究在国际上首次报道了LCE基因簇为银屑病的易感位点。目的:对寻常型银屑病发病年龄、家族史及临床类型进行分层分析,在汉族人群中研究寻常型银屑病LCE3D基因多态性（rs4085613）位点与临床表型的相关性,为进一步探讨银屑病的发病机制提供重要的遗传学依据。方法:1,139例PV患者和1,132例正常对照的LCE3D基因多态性rs4085613位点基因分型（AA、AC、CC）资料均来源于本课题组银屑病全基因组关联分析的Illumina 610芯片分型数据,数据资料经适当转化后应用社会科学统计软件包SPSS 15.0对资料进行统计学分析。结果:1.病例组与对照组的基因型总体分布差异具有统计学意义(χ²=33.71,df=2,P=4.79×10^-8),病例组与对照组的等位基因分布差异亦具有统计学意义(χ²=31.85,df=1,P=1.67×10^-8,OR 1.41,95%CI 1.25-1.59)。2.少儿发病患者与对照比较,rs4085613位点基因型和等位基因分布差异均有统计学意义(χ²=14.48,df=2,P=0.001;χ²=12.86,df=1,P=3.35×10^-4,OR 1.38,95%CI 1.16-1.65)。成人发病患者与对照比较,rs4085613位点基因型和等位基因分布差异亦具有统计学意义(χ²=27.99,df=2,P=8.36×10^-7;χ²=27.35,df=1,P=1.70×10^-7,OR 1.42,95%CI 1.25-1.62)。少儿发病患者和成人发病患者间rs4085613位点基因型和等位基因分布差异均无统计学意义（χ²=1.10,df=2,P=0.58;χ²=0.08,df=1,P=0.78,OR 0.97,95%CI 0.81-1.17）。比较各发病年龄段LCE3D基因rs4085613位点基因型频率无显著性差异（P>0.05）。3.家族史阳性患者与对照比较,rs4085613位点基因型和等位基因分布差异均有统计学意义（χ²=19.70,df=2,P=5.27×10-5;χ²=19.19,df=1,P=1.18×10-5,OR 1.44,95%CI 1.22-1.69）。家族史阴性患者与对照比较,rs4085613位点基因型和等位基因分布差异亦具有统计学意义(χ²=24.15,df=2,P=5.71×10^-6;χ²=23.02,df=1,P=1.60×10^-6,OR 1.40,95%CI 1.22-1.61)。家族史阳性患者和阴性患者间rs4085613位点基因型和等位基因分布差异均无统计学意义（χ²=0.11,df=2,P=0.95;χ²=0.09,df=1,P=0.77,OR 1.03,95%CI 0.86-1.23）。4.急性点滴型患者与对照比较,rs4085613位点基因型和等位基因分布差异均有统计学意义（χ²=13.83,df=2,P=0.001;χ²=10.71,df=1,P=0.001,OR 1.33,95%CI 1.12-1.57）。慢性斑块型患者与对照比较,rs4085613位点基因型和等位基因分布差异亦具有统计学意义(χ²=30.41,df=2,P=2.50×10^-7;χ²=30.01,df=1,P=4.30×10-8,OR 1.46,95%CI 1.27-1.67)。急性点滴型患者与慢性斑块型患者间rs4085613位点基因型和等位基因分布差异均无统计学意义（χ²=3.95,df=2,P=0.14;χ²=1.04,df=1,P=0.31,OR 0.91,95%CI 0.76-1.09）。结论:1. LCE3D基因rs4085613遗传多态性与汉族人寻常型银屑病的易感性相关。2.汉族人PV患者的发病高峰在15-30岁之间,LCE3D基因rs4085613遗传多态性与PV的发病年龄无明显相关性。3. 1型PV患者家族史的阳性率高于2型PV患者,LCE3D基因rs4085613遗传多态性与PV的有无家族史无明显相关性。4. LCE3D基因rs4085613遗传多态性与PV的临床发病类型无明显相关性。5. LCE3D基因rs4085613遗传多态性均对PV的发病年龄、有无家族史以及发病类型的影响作用较弱,可能与银屑病具有不同的遗传学基础和不同的发病机制有关。更多还原

【Abstract】 Background Psoriasis （OMIM#177900） is a common, chronic and recurrent, inflammatory skin disease. Both genetic and environmental factors play important roles in the pathogenesis of psoriasis. Psoriasis vulgaris （PV） is the most frequent clinical type. We found a distinguished correlation of rs3213094 polymorphism in LCE gene cluster with psoriasis vulgaris in Chinese Han Population by psoriasis genome-wide association study （GWAS）.Objective Based on stratifying analysis of the age of onset, family history and clinical types, the study compared the genotype distribution of rs4085613 polymorphism within LCE3D gene with some clinical features of psoriasis vulgaris in the Han Chinese population in order to further explore the genetics pathogenesis.Methods We analyzed the distributions of genotype and allele of rs4085613 polymorphism within LCE3D gene in 1,139 cases and 1,132 normal controls, which derived from the psoriasis genome-wide association study （GWAS）. The appropriate application of social science statistical software package SPSS 15.0 was used for statistical analysis of data.Results 1. The genotype frequency of rs4085613 polymorphism within LCE3D gene was of statistical significance between the cases and the controls （χ²=33.71, df=2, P=4.79×10-8）, there was a similar trend for the allelic frequency （χ²=31.85, df=1,P=1.67×10-8, OR 1.41, 95%CI 1.25-1.59）. 2. The genotype and allelic frequencies of rs4085613 polymorphism were statistical significance between the pediatric age of onset cases and controls （χ²=14.48, df=2, P=0.001;χ²=12.86, df=1, P=3.35×10-4, OR 1.38, 95%CI 1.16-1.65）. The genotype and allelic frequencies of rs4085613 polymorphism were also statistical significance between the adult age of onset cases and controls (χ²=27.99, df=2, P=8.36×10^-7;χ²=27.35, df=1, P=1.70×10^-7, OR 1.42, 95%CI 1.25-1.62). However, there weren’t statistical significance between the pediatric age of onset and adult age of onset cases （χ²=1.10, df=2, P=0.58;χ²=0.08, df=1, P=0.78, OR 0.9, 95%CI 0.81-1.17）. Meanwhile, there wasn’t significant difference among the age of onset for the rs4085613 genotype frequency （all P>0.05）. 3. The genotype and allelic frequencies of rs4085613 polymorphism within LCE3D gene were statistical significance between the familial cases and controls （χ²=19.70, df=2, P=5.27×10-5;χ²=19.19, df=1, P=1.18×10-5, OR 1.44, 95%CI 1.22-1.69）. The genotype and allelic frequencies of rs4085613 polymorphism were also statistical significance between the sporadic cases and controls (χ²=24.14, df=2, P=5.71×10^-6;χ²=23.02, df=1, P=1.60×10^-6, OR 1.40, 95%CI 1.22-1.61). However, there weren’t statistical significance between the familial and sporadic cases （χ²=0.11, df=2, P=0.95;χ²=0.09, df=1, P=0.77, OR 1.03, 95%CI 0.86-1.23）. 4. The genotype and allelic frequencies of rs4085613 polymorphism LCE3D gene were statistical significance between the acute guttate cases and controls （χ²=13.83, df=2, P=0.001;χ²=10.71, df=1, P=0.001, OR 1.33, 95%CI 1.12-1.57）. The genotype and allelic frequencies of rs4085613 polymorphism were also statistical significance between the chronic plaque cases and controls (χ²=30.41, df=2, P=2.50×10^-7;χ²=30.01, df=1, P=4.30×10^-8, OR 1.46, 95%CI 1.27-1.67). However, there weren’t statistical significance between the acute guttate and chronic plaque cases （χ²=3.95, df=2, P=0.14;χ²=1.04, df=1, P=0.31, OR 0.91, 95%CI 0.76-1.09）. Conclusions 1. The rs4085613 polymorphism within LCE3D gene is associated with the susceptibility of psoriasis vulgaris in the Han Chinese population. 2. PV patients with a peak incidence at 15-30 years of age, the rs4085613 polymorphism within LCE3D gene isn’t associated with age of onset of psoriasis vulgaris. 3. The family history positive rate PV patients in the type 1 is higher than the sporadic PV patients in type 2, the rs4085613 polymorphism within LCE3D gene isn’t associated with family history of psoriasis vulgaris. 4. The rs4085613 polymorphism within LCE3D gene isn’t associated with clinical type of psoriasis vulgaris. 5. Our findings indicated that the rs4085613 polymorphism within LCE3D gene may have no effected on the age of onset, family history and clinical type, which maybe associate with different psoriasis genetic basis and pathogenesis.更多还原