Association Study On Alopecia Areata Susceptibility Loci Of Caucasians In Chinese Han Population

Background Alopecia areata (AA) is a nonscarring, inflammatory skin disease thatresults in patchy hair loss.The areas of skin with hair loss are smooth, have a naturalcolor or slightly pink/peach tone. The hair loss can presents single delimited patches ofair loss (most common),multiple patches, or extensive hair loss.The hair fibers at theborder of these patches may have an “exclamation mark” appearance: short, broken hairfibers with a broader distal end compared to the proximal end.AA can occur on virtuallyany hair-bearing area, but it affects the scalp in approximately90%of caucasians indermatology clinics.Although alopecia is not painful or life-threatening, the hair lossitself—especially its unpredictable course-causes substantial psychological distress inthe majority of those affected. It also lead to profound emotional stress and reducedself-esteem.The pathogenesis of AA is not entirely understood. Study have showed that the effectof genetic factors is strong in AA, but environmental factors such as infection andpsychological stress may still play an important role.As a new method GWAS has madesome progress in the genetics of common complex diseases.With the help of GWAS, thesusceptibility genes of more than60complex diseases have been revealed,which areimportant and complicated diseases to human life and health,including type I, type IIdiabetes, prostate cancer, colorectal cancer, breast cancer, systemic lupus erythematosus,coronary heart disease, gallstones, obesity.The first genome-wide association study(GWAS) of AA in a sample of1,054cases (US patients of self-reported Europeanancestry) and3,278controls and identified139single nucleotide polymorphisms (SNPs)that are significantly associated with AA (P≤5×107). These susceptibility loci includethe following genes: cytotoxic T lymphocyte–associated antigen4(CTLA4), IL-2/IL-21,IL-2receptor A(IL-2RA;CD25) peroxiredoxin5(PRDX5), syntaxin17(STX17), thegenes Eos (also known as Ikaros family zinc-finger4; IKZF4) and the erythroblasticleukemia viral oncogene homolog3(ERBB3),cytomegalovirus UL16–binding protein(ULBP) and several genes in the HLA region. So far,there is still no GWAS in Chinese Han,it’s important to replicate these SNP in Chinese Han cases.Objective The aims of our study were to provide independent replication of thegenome-wide significant loci identified in the recent US GWAS,14SNPs from the USGWAS were selected.Methods We replicated these SNPs in Chinese Han (1104cases/1840controls) usingSequenom Massarray system.14SNPs from the US GWAS were selected. PLINK1.07were used for Statistical analysis. P≤0.05is considered to be significant.Results In our sample, no significant differences in allele or genotype frequencies wereobserved between cases and controls for any of the investigated SNPs.Only one SNPachieved nominal significance [rs9479482,P=0.032; odds ratio (OR)1.16; confidenceinterval (CI)1.01–1.33;Pc=0.42].,but the results remained negative after corrected byBonferroni’s method (Pc=0.42).Conclusions The results indicated that14SNPs including rs1024161，rs231804inCTLA4，rs3096866in ICOS，rs10760706in STX17, rs10876864，rs1701704andrs2069408in IKZF4，rs705708in ERBB3，rs12213837in ULBP3，rs9479482inULBP6，rs3118470and rs4147359in IL-2RA，rs694739in PRDX5may not beassociated with AA in Chinese Han population. Further study in a larger Chinese Hansample should be performed.