斑秃易感位点与中国汉族人群相关性研究

Association study of alopecia areata susceptibility loci in Han Chinese population

目的：研究国外斑秃人群已发现的易感基因与中国汉族人群斑秃的相关性。方法选择736例斑秃患者和1840例对照者,提取基因组 DNA,利用 Sequenom Massarray系统,对国外报道的斑秃易感基因位点[17个单核苷酸多态性（SNPs）]进行验证,用 Plink 1．07软件对基因型进行关联分析。结果 CTLA4基因上 rs3087243（ P =0．041, OR =1．18,95% CI =1．01-1．38）,经 Bonferroni 校正后无显著相关性（Pc =0．697）,其余16个位点（ TLR1、DMBT1、CHIT1、GBP4、 CIITA、 IL31RA、 CD96、 INPPL1、 MASP2、 IL-13、 KI-AA0350、PTPN22、SPATA5、TRAF1/ C5、IL1A、IL2RA）等位基因频率在病例组和对照组之间差异无统计学意义（ P 〉0．05）；分层分析显示发病年龄〉20岁与≤20岁两组之间比较, TRAF1基因中 rs2416808位点（P =0．0184, OR =1．35,95% CI =1．05-1．74）；轻型与重型斑秃、有无家族史,等位基因频率在两两之间比较差异均无统计学意义（P 〉0．05）。结论国外报道的17个 SNPs 与中国汉族人群的斑秃没有显著相关性,不同人群之间可能存在遗传异质性,进一步的研究需要在较大的斑秃样本中进行。

Objective To study the correlation between alopecia areata and the susceptibility genes identified in our previous study with Han Chinese population. Methods The study performed an independent replication study using 736 cases and 1 840 controls. DNA was extracted from peripheral blood leukocytes by salting out with saturat-ed NaCl solution according to standard methods. The evidence for association had been obtained from former gene study. Then a fine-mapping study and genotyped the locus with an additional 17 SNPs were performed. Data were analyzed with the use of Plink 1. 07 software. Results Only one SNP achieved nominal significance, rs3087243 （P = 0. 041, OR = 1. 18, 95% CI = 1. 01 - 1. 38）. The other 16 genes （TLR1, DMBT1, CHIT1, GBP4, CIITA, IL31RA, CD96, INPPL1, MASP2, IL-13, KIAA0350, PTPN22, SPATA5, TRAF1 / C5, IL1A, IL2R） failed. A further stratification analysis of alopecia areata was adopted, including the analysis of family history, the age of on-set and the severity of alopecia areata. The stratification analysis revealed that the age of onset 〉 20 years achieved nominal significance P 〈 0. 05 for one SNP, rs2416808 （P = 0. 018, OR = 1. 35, 95% CI = 1. 05 - 1. 74）, where-as, the other results were of no statistical significance. Conclusion The results indicate that 17 SNPs may not be associated with AA in Han Chinese population. Further study should be performed in a larger Han Chinese sam-ples.