Study On The Susceptible Genes Of Congenital Bilateral Absence Of The Vas Deferens In Male Han Chinese Population

Background: Cystic fibrosis (CF) is a common, monogenic, autosomalrecessive disorder. It occurs as a result of mutations in the cystic fibrosistransmembrane conductance regulator (CFTR) gene.The clinicalmanifestation including progressive lung failure，pancreatic insufficiencyand infertility. As a result of the isolated primary genital presentation ofcystic fibrosis (CF), CBAVD occurs in95%of male sufferers with CF andin1-2%of the whole infertile males. Numerous studies have demonstratedthat CF and CBAVD are caused by genetic factors. CFTR gene wasdetected as candidate gene from78%of the patients. But an increasingnumber of other candidate genes involved in CF and CBAVD have beingreported.Endothelin receptor type A (EDNRA)，Epithelial sodium channel（ENaC）and the proinflammatory cytokines interleukin1β(IL-1β) are respectivelypaly an important role in cystic fibrous patients. Further studies showedthat EDNRA plays an important role in the formation of the bilateral vasdeferens. A confrontational interaction on regulation of the airway surfaceliquid balance was revealed between cystic fibrosis transmembrane conductance regulator （CFTR）and ENaC. IL-1β could improved theamount of CFTR in airway cells.Objective: Our study aimed to demonstrate whether EDNRA, ENaC andIL-1β gene polymorphisms are the risk factors at the development ofcongenital bilateral absence of the vas deferens (CBAVD).Methods: This case-control study contained124patients with congenitalbilateral absence of the vas deferens (CBAVD) and103fertile males.Genomic DNA was extracted from peripheral venous blood leukocytesusing QIAamp genomic DNA kits (Qiagen, Hilden, Germany). PCRamplification primers for the four single-nucleotide polymorphisms (SNPs)including EDNRA gene (rs5335, rs1801708), SCNN1G gene (rs5735) andIL1B gene (rs3917356) were respectively designed using GENETOOLsoftware and genotyped by polymerase chain reaction and restrictionfragment length polymorphism (PCR-RFLP) analysis and directsequencing.Results: No significant differences between EDNRA gene、SCNN1G gene、IL1B gene polymorphisms and CBAVD phenotype (χ~2=2.9945, df=2, P=0.2237, rs1801708; χ~2=0.1951, df=2, P=0.9070, rs5335；χ~2=1.3536, df=2, P=0.5082, rs5735; χ~2=2.1703, df=2, P=0.3378, rs3917356) were observed. But the rs1801708-rs5335haplotype AG was observed as asignificantly increased risk of CBAVD (P=0.0086, OR=2.178,). Thers1801708-rs5335haplotype GG was observed as a significantly protectiveeffect on CBAVD (P=0.0385, OR=0.671).Conclusions: Thus the rs1801708-rs5335haplotype AG of the EDNRAgene could be identified as a risk factor for CBAVD development in theChinese Han male with bilateral absence of the vas deferens. Thers1801708-rs5335haplotype GG may play a protective effect on theformation of the bilateral vas deferens. The SNPs polymorphisms of theSCNN1G and IL1B gene may not considered as the risk factors for theCBAVD development in Chinese group.