Association Study On Androgenetic Alopecia Susceptibility Loci Of Caucasians In Chinese Han Populaiton

Background Androgenetic alopecia (AGA) is the most common disease with hair lossin humans, Which is generally classified into male androgenetic alopecia (MAGA) andfemale pattern hair loss (FPHL). MAGA is characterized by a recession of the frontalhair line, mainly in a triangular pattern, later followed by a vertex thinning. FPHL ischaracterized by a diffuse thinning of the centro-parietal region with preserving thefrontal hair line. The prevalence of AGA is different among races (3.5%-50%), it washigher in Caucasians than in Africans and Asian populations. In China, the prevalenceof AGA was21.3%in men and6.0%in women. Although the exact pathogenesis ofAGA remains unclearly, genetic factors and androgens have been demonstrated to playimportant roles in the development of AGA. With the recent advent of the genome-wideassociation studies (GWAS), several susceptibility loci have been found to beassociated with AGA. The major genetic risk loci for AGA in Caucasians includeAR/EDA2R locus on X-chromosomal, HDAC9locus on chromosome7p21.1, and locuson chromosome20p11. The above3susceptibility loci have been replicated in theChinese Han population in our previous study. We observed that a locus onchromosome20p11was strongly associated with MAGA. Recently, Li et al conducted alarge-scale meta-analysis of seven GWAS for early-onset AGA with12,806individualsof European ancestry, and found six novel susceptibility gene/loci (TARDBP, HDAC4,HDAC9, AUTS2,17q21.31, SETBP1). Heilmann et al identified four novelgenome-wide significant risk loci for AGA through combined analysis of the replicationand the meta-analysis data (2q35,3q25.1,5q33.3,12p12.1). Due to the existence of the genetic heterogeneity among different races, and the most of related research mainlyfocus on Caucasians. Therefore, the association between these reported susceptibilityloci and AGA in Chinese Han population is unclear.Objectives To find the susceptibility loci with AGA in the Chinese Han population. Thereported susceptibility loci of AGA from Caucasians were replicated in the Chinese Hanpopulation by association analyses.Methods Thirteen susceptibility loci (including18single nucleotide polymorphisms)for AGA from Caucasians were genotyped in a Chinese Han cohorts (total368patientswith MAGA and746controls) by using the Sequenom Massarray system. ThePlink1.07software was used to test the association analyses.Results There was no significant differences for the18SNPs by comparing the MAFbetween cases and normal controls (Pc＞0.05). There was significant MAF differencefor the SNP rs3786939between the case group with positive family history and thenormal control group (P=0.008, OR=1.459,95%CI=1.102-1.931). There was nosignificant MAF difference for this SNP between the case group without family historyand the normal control group (rs3786939, P=0.595, OR=0.932,95%CI=0.717-1.210).There was significant MAF difference for this SNP between the case group withpositive family history and the case group without family history (rs3786939, P=0.010,OR=1.566,95%CI=1.112-2.205). But the total results remained negative aftercorrected by Bonferroni’s method（Pc＞0.05）. There was significant MAF differencefor the SNP rs9752491between the case group with disease severity≥Ⅳ and the normalcontrol group (P=0.007, OR=1.588,95%CI=1.134-2.224). There was no significantMAF difference for this SNP between the case group with disease severityⅠ-Ⅲ and thenormal control group (rs9752491, P=0.874, OR=1.023,95%CI=0.774-1.351). There was significant difference between the case group with disease severity≥Ⅳ and thecase group with disease severityⅠ-Ⅲ (rs9752491, P=0.026, OR=1.553,95%CI=1.052-2.292). But the total results remained negative after corrected by Bonferroni’smethod (Pc＞0.05).Conclusions This study did not find any association between MAGA and the18SNPs.But we can not affirm that there is no association between the13susceptibilitygene/loci and MAGA. We speculate that there are genetic heterogeneity between theChinese Han population and the Caucasian population. Fine mapping study will beneeded to perform for these loci, and the enlargement of the samples is needed toreplicate in further studies.