【作者】 方芳；

【导师】 张安平； 唐先发；

【作者基本信息】 安徽医科大学 ， 皮肤性病学科， 2018， 硕士

【摘要】 研究背景白癜风是皮肤中黑素细胞消失所引起的一种常见的获得性或全身性皮肤色素脱失症,但其机制尚不清楚,可能与免疫,遗传和获得性环境的相互作用有关。GWAS广泛用于白癜风基因研究领域。到目前为止,有许多来源于GWAS研究的白癜风相关基因和位点。不同国家和种族的白癜风相关基因存在差异。在欧洲人群中,白癜风相关基因/位点包括1p13.2(PTPN22,rs2476601),1p36.23(RERE,rs4908760),2q24.2(IFIH1,rs2111485),3q13.33(CD80,rs59374417),3q28LPP,rs1464510),4p16.1(CLNK,rs16872571),6p21.32(C6orf10,BTNL2,rs7758128BTNL2,HLA-DRA,rs3806156),8q24.22(SLA,rs853308),10p15.1(IL2RA,rs706779),10q25.3(CASP7,rs3814231)11p13(CD44,rs10768122),11q14.3(TYR,rs1393350)11q21(TYR,rs4409785),12q13.2(IKZF4,rs2456973),12q24.12(SH23,rs4766578)14q12(GZMB,rs8192917,rs2273844)15q13.1(OCA2,HERC2,rs1129038),16q24.3(MC1R,rs9926296),19p13.3(TICAM1,rs6510827),21q22.3(UBASH3A,rs11203203),22q13.1(C1QTNF6,rs229527),22q13.2(TOB2,rs4822024)。在中国汉族人群中,白癜风相关基因/位点包括3q28(LPP,rs9851967)11q23.3(CXCR5,DDX6 rs638893)12q13.2(PMEL,IKZF4,rs10876864)。最近的研究发现欧美患者白癜风中存在一些新的风险位点,包括rs6583331,rs41342147,rs1031034,rs35161626,rs6059655,rs231725,rs6012953,rs12421615,rs16843742,rs8083511,rs4807000,rs11079035,rs4308124,rs78037977,但这些位点在中国汉族白癜风患者中尚未发现。因此,我们对中国汉族人群白癜风患者的进行这些位点验证,研究了这些位点与汉族人群的相关性,为白癜风的研究提供了新的线索。目的我们的实验将验证新发现的14个位点,并研究这些新的位点是否与汉族人群白癜风发病有关。为白癜风的发病原因找到新的突破口。方法收集1472例病例和1472例健康对照,设计SNP引物,并使用Sequenom Mass Array对14个SNPs进行基因分型并输出结果,运用PLINK1.70进行SNP等位基因分布频率的关联研究,运用SPASS17.0进行数据整理结果的统计学分析。结果rs6583331位于染色体3q29 FBXO45-NRROS基因区域,rs6583331 T等位基因与中国汉族白癜风人群有显著相关性(OR=1.22,95%CI:1.10-1.36,P=0.0001);rs6583331的T等位基因在中国汉族白癜风人群中以显性模式遗传占有优势(P=0.0007)。结论该研究揭示了rs6583331与中国汉族人群白癜风相关。为深入探索rs6583331与白癜风的关系奠定了基础。同时为研究FBXO45-NRROS基因区域与白癜风关系带来新的启示,其中的分子机制有待进一步实验研究发现。更多还原

【Abstract】 Background Vitiligo is a common acquired or generalized skin depigmentation disease caused by the disappearance of melanocytes in the skin,but the mechanism is not yet clear and may be related to the interaction of immune,hereditary and acquired environment.GWAS is widely used in the field of vitiligo gene research.So far,there are many vitiligo-related genes and loci derived from GWAS studies.There are differences in vitiligo-related genes among different nations and races.In the European population,vitiligo-related genes/loci include 1p13.2(PTPN22,rs2476601),1p36.23(RERE,rs4908760),2q24.2(IFIH1,rs2111485),3q13.33(CD80,rs59374417),3q28(LPP,rs1464510),4p16.1(CLNK,rs16872571),6p21.32(C6orf10,BTNL2,rs7758128 BTNL2,HLA-DRA,rs3806156),8q24.22(SLA,rs853308),10p15.1(IL2RA,rs706779),10q25.3(CASP7,rs3814231)11p13(CD44,rs10768122),11q14.3(TYR,rs1393350)11q21(TY R,rs4409785),12q13.2(IKZF4,rs2456973),12q24.12(SH23,rs4766578)14q12(GZMB,rs8192917,rs2273844)15q13.1(OCA2,HERC2,rs1129038),16q24.3(MC1R,rs9926296),19p13.3(TICAM1,rs6510827),21q22.3(UBASH3A,rs11203203),22q13.1(C1QTNF6,rs229527),22q13.2(TOB2,rs4822024)。 In the Chinese Han population,vitiligo-related genes/loci include 3q28(LPP,rs9851967)11q23.3(CXCR5,DDX6 rs638893)12q13.2(PMEL,IKZF4,rs10876864)。Recent studies have found some new risk loci in the European and American patients with vitiligo,including rs6583331,rs41342147,rs1031034,rs35161626,rs6059655,rs231725,rs6012953,rs12421615,rs16843742,rs8083511,rs4807000,rs11079035,rs4308124,rs78037977,but these loci have not been found in Chinese Han patients with vitiligo.Therefore,we validated these loci in Chinese Han population with vitiligo to study which of these loci are related to Han population and provide a new clue for vitiligo research.Objective Our experiment will verify the newly discovered 14 sites and study whether these new sites are related to the incidence of vitiligo in the Han population and find a new breakthrough in the pathogenesis of vitiligo.Methods 1472 cases and 1472 healthy controls were collected,SNP primers were designed,and 14 SNPs were genotyped and output using Sequenom Mass Array.Plink 1.70 was used for the association study of SNP allele frequencies,using SPASS 17.0.Statistical analysis of data consolidation resultsResults rs6583331 is located in the region of chromosomal 3q29 FBXO45-NRROS gene,and the rs6583331 T allele is significantly associated with Chinese Han people with vitiligo(OR = 1.22,95% CI: 1.10-1.36,P = 0.0001);the rs6583331 T allele is in China.The Han nationality has a preponderance of dominant inheritance in the vitiligo population(P=0.0007).Conclusion The study revealed that rs6583331 is associated with vitiligo in the Chinese Han population.In order to further explore the relationship between rs6583331 and vitiligo laid the foundation.At the same time,it has brought new enlightenment to the study of the relationship between FBXO45-NRROS gene region and vitiligo.The molecular mechanism needs further experimental research.更多还原