转录因子叉状头螺旋转录因子3基因多态性与贵州汉族斑秃的相关性研究  

Study on association between FOXP3 gene polymorphism and alopecia areata in Chinese Han population of Guizhou province

作　　者：杨莹 梁翰月 陈晓红 杨英 陈林 陈永艳 晏文 YANG Ying;LIANG Han-yue;CHEN Xiao-hong;YANG Ying;CHEN Lin;CHEN Yong-yan;YAN Wen(Department of Dermatology,Affiliated Hospital of Medical College Zunyi,Zunyi 563003,China)

机构地区：[1]遵义医科大学附属医院皮肤科,贵州遵义563003 [2]贵州茅台医院皮肤科,贵州仁怀564500 [3]遵义医科大学第二附属医院皮肤科,贵州遵义563000 [4]贵州航天医院皮肤科,贵州遵义563000

出　　处：《临床皮肤科杂志》2021年第9期521-530,共10页Journal of Clinical Dermatology

基　　金：遵义市科学技术基金[遵市科合社字(2014)84号];贵州省卫计委科技基金(gzwjkj2017-1-040);贵州省科技厅联合基金(黔科合LH字[2015]7474号);贵州省中医药管理局科技基金(QZYY-2015-039);遵义市科合HZ字(2020)219号。

摘　　要：目的:探讨贵州汉族人群转录因子叉状头螺旋转录因子(FOXP)3与斑秃易感性和疾病表型的关联。方法:选取250例斑秃患者作为患者组,200例健康人作为对照组,利用Snapshot技术检测研究对象中FOXP3基因rs3761547、rs3761548、rs3761549、rs2232365位点的基因型,并进行连锁不平衡分析和单体型构建。结果 :FOXP3基因4个SNP位点(rs3761547、rs3761548、rs3761549、rs2232365)的基因型及等位基因频率在斑秃与健康对照组间差异具有统计学意义(P值均≤0.001),4个SNP位点在隐性和累加遗传模式下,斑秃组与健康对照组间基因型频率差异具有统计学意义(P<0.001),rs3761547和rs2232365位点G等位基因、rs3761548位点A等位基因、rs3761549位点T等位基因均可能增加贵州汉族斑秃患病的风险,携带G、A及T等位基因者可能更易患斑秃。临床表型的关联分析:rs3761547等位基因与男女性别相关,预示着携带A等位基因的男性斑秃患者发病风险会减小;rs3761549等位基因与首次发病年龄相关,预示着携带C等位基因在年龄<30岁斑秃患者发病风险会减小;4个SNP位点与斑秃的复发与否、活动性、病程及病情严重程度均无相关性。连锁不平衡和单体型分析:4个SNP位点间存在连锁不平衡(D′=0.273~1,r2=0.002~0.419)。且4个SNP位点构建10种单倍型,分析每个单倍型频率的分布,发现4个单倍型(AACG、ACCA、GCCG、GCTG、ACTA)在斑秃病例组与正常对照组间差异具有显著统计学意义(P均<0.05),携带单体型AACG(OR:1.636;95%CI:1.103~2.425)和GCCG (OR:33.159;95%CI:8.074~136.178)者更易患斑秃。结论:FOXP3基因(rs3761547、rs3761548、rs3761549、rs2232365)位点多态性与贵州汉族人群斑秃具有相关性,FOXP3基因多态性在不同临床表型中可能发挥着不同的作用,进一步的研究需要在较大的斑秃样本中进行。Objective: To explore the association between FOXP3 gene polymorphisms and susceptibility to develop alopecia areata, as well as clinical phenotype of alopecia areata in Chines Han population of Guizhou province. Methods: Total 250 patients with alopecia areata were selected as the patient group, and 200 healthy individuals were included as the control group. Snapshot technology was used to detect the four SNPs of FOXP3 gene including rs3761547, rs3761548, rs3761549 and rs2232365. Linkage disequilibrium analysis and haplotypes were constructed. Results: The genotypes and allele frequencies of the 4 SNP loci(rs3761547, rs3761548, rs3761549, rs2232365) of the FOXP3 gene were significantly different between the patient group and the control group(P≤0.001). Under the recessive inherited and additive effect, the difference in the genotypes and frequencies of all 4 SNP loci between the patient group and the control group was statistically significant(P<0.001).The G allele at rs3761547 and rs2232365, the A allele at rs3761548, and the T allele at rs3761549 could increase the risk to develop alopecia areata in Chinese Han population of Guizhou. Those who carry the G, A, and T alleles may be more susceptible to alopecia areata. Analysis of association between FOXP3 gene and clinical phenotype of alopecia areata showed that rs3761547 allele was related to gender, and the risk of the male carrying the A allele to develop alopecia areata would be reduced. The rs3761549 allele was related to the age at the first onset, and the risk of the individual carrying C allele to develop alopecia areata at the age younger than 30 years old would be reduced. There was no association between the 4 SNP loci and the recurrence, activity, course and severity of alopecia areata. Analysis of linkage disequilibrium and haplotype showed that there was linkage disequilibrium among the 4 SNP loci(D′=0.273~1, r2=0.002~0.419). Ten haplotypes were constructed by4 SNP sites, and the frequency distribution of each haplotype was analyzed. Four hapl

关 键 词：FOXP3基因 贵州汉族 斑秃 单核苷酸多态性 连锁不平衡 单体型 

分 类 号：R758.71[医药卫生—皮肤病学与性病学]