Association Study Of Alopecia Areata Susceptibility Loci In Han Chinese Population

Background Alopecia areata(AA) is a nonscarring, in?ammatory skin disease that results in patchy hair loss. The hair loss can presents single delimited patches(most common), multiple patches and extensive hair loss. It is unpredictable course causes substantial psychological distress in the majority of those affected individuals, which could led to profound emotional stress and reduced self-esteem. So far, the disease pathogenesis is not entirely understood. Studies have shown that AA has a genetically complex inheritance that implicated by the familial aggregation phenomenon. The prevalence of alopecia areata was about 0.1%-0.2% at abroad, while 0.27% in China,and the prevalence rate in male is thought to be around 1.7%, regardless of demographical location, whlch is significantly higher than female. Alopecia areata is a complex genetic, immune-mediated disease that targets anagen hair follicles. The disease affects both children and adults. Alopecia areata is generally divided into eight types. It is commonly characterized by round or oval patches of hair loss, loss of all scalp hair(alopecia totalis), body hair(alopecia universalis), or ophiasis pattern hair loss.Patients may also present with patchy loss in multiple hair-bearing areas. AA is often accompany with other disease, including asthma, allergic rhinitis, atopic dermatitis,thyroid disease, and automimmune diseases, such as DM, vitiligo. Because of the different research methods and materials, the significant of results are differences, so it is necessary to identify the susceptibility genes of alopecia areata for several times.Sixteen significance SNPs were selected on the basis of the results of Asians and Caucasians GWAS, exome sequencing and candidate gene. These genes are respectively located in TLR1, DMBT1, CHIT1, GBP4, CIITA, IL31 RA, CD96, INPPL1, MASP2,IL-13, KIAA0350, PTPN22, SPATA5, TRAF1 ?C5, IL1 A, IL2 RA, CTLA4. At present,there are a number of studies have verified the susceptibility genes that reported in GWAS of alopecia areata. Due to the genetic heterogeneity exists in different ethnic groups, more than one team in our country have verified the susceptibility genes of alopecia areata for many times.Objective To identify new genetic variants and further explain the genetic basis of alopecia areata, the aims of our study were to provide independent replication of the genome-wide significant loci to confirm that whether these genes are associated with AA or not.Methods We performed an independent replication study in 736 cases and 1,840 controls. DNA was extracted from peripheral blood leukocytes by salting out with saturated Na Cl solution according to standard methods. The evidence for association had been obtained from former genetic study. Then, we genotyped the locus with an additional 16 SNPs, and analyzed the data with the Plink 1.07 software. P value is less than 0.05 that was considered statistically significant.Results Sixteen significance SNPs were selected on the basis of the results of the Asians and Caucasians GWAS, exome sequencing and candidate gene. Only one SNP achieved nominal signi?cance,rs3087243 [CTLA4, P=0.04116, odds ratio(OR) =1.18,con?dence interval(CI) =1.01~1.38]. We also intend to adopt stratification analysis of alopecia areata, including the analysis of subgroups of individuals with a positive family history, the age at onset was>20 years and severe alopecia areata. The analysis ofsubgroups of individuals with the age at onset was>20 years revealed, P < 0.05 for one SNP, rs2416808 [TRAF1, P=0.0184, odds ratio(OR) =1.35, con?dence interval(CI)=1.05~1.74]; Between mild AA and severe AA, rs2277244 [DMBT1, P=0.08617,OR=1.54(0.94~2.52)], P<0.1; It shows that the correlation between DMBT1 and severe alopecia areata has implications; The analysis of subgroups of individuals with a positive family history of the disease revealed, P>0.05; The analysis of subgroups of individuals with gender revealed, P>0.05.Conclusion The results indicated that 16 SNPs may not be associated with AA in Han Chinese population. Further study should be performed in a larger Han Chinese samples.