ERBB4 Confers Risk For Polycystic Ovary Syndrome In Han Chinese

Background:Polycystic Ovary Syndrome(PCOS)is the most common endocrinopathy of reproductive-aged women.It is a heterogeneous disorder defined by three cardinal clinical features:oligo-ovulation/anovulation(OA),clinical and/or biochemical hyperandrogenism(HA)and polycystic morphology of the ovaries(PCOM).At the same time,it accompanied by insulin resistance,obesity,and has an increased risk of diabetes,cardiovascular disease and metabolic syndrome.PCOS has a significant impact to the health of women's lifetime.Genome-wide association studies(GWAS)is an effective way to found risk genes of complex disease.A recent genome-wide association study(GWAS)of polycystic ovary syndrome(PCOS)in European cohorts has identified six susceptibility loci mapping to 11q22.1(YAP1)2p21(THADA),llpl4.1(FSHB),2q34(ERBB4),12q21.2(KRR1),and 5q31.1(RAD50).The loci of 11q22.1,2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese;whereas the other three new loci(2q34,12q21.2,and 5q31.1)still need to be evaluated in Chinese.Objective:This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese.Methods:We performed a case-control genetic association study comprising 1500 PCOS cases and 1220 age-matched control subjects.Marker SNPs rs 1351592(2q34,ERBB4),rs1275468(12q21.2,KRR1)and rs13164856(5q31.1,RAD50)were genotyped using TaqMan-MGB probe assay;and the associations with PCOS,endocrine and metabolic traits were assessed.Resuls:Genotyping analysis showed the allele frequency of rs1351592 in gene ERBB4 was significantly different(P= 1.05×10-3)between PCOS cases and control group,and remained significant even after BMI adjustment(Padjusted=2.09×10-4).However,the allele frequencies of the other two risk variants,rs 1275468(12q21.2,KRR1)and rs13164856(5q31.1,RAD50),were not significantly different in the replication cohort.No association was observed among hormonal and metabolic parameters(FSH,LH,T,DHEAS,FG,FINS,and HOMA-IR)between rs1351592 risk allele group and non-risk allele group.Conclusion:Our results demonstrate that ERBB4,with the strongest association in European PCOS,also confers risk for PCOS in Han Chinese.