Association Study Between Single Nucleotide Polymorphism Of P73 And EPSTI1 Gene With Dyszoospermia

Infertility is a worldwide problem,it is the third difficult problem after tumor and cardiovascular and cerebrovascular diseases.The incidence of the childbearing couples in reproductive age is as high as 10 % ~ 15 %,of which 50 % male is males.The etiology of male infertility is complex,except endocrine hormone disorder,reproductive tract inflammation,varicocele,immune abnormality,physical and chemical factors,spermatogenic dysfunction is one of the most common types in male infertility.Studies have shown that genetic factors play an important role in spermatogenesis failure.At present,there are some genetic factors related to spermatogenesis,such as chromosome aberration,Y chromosome microdeletion and gene mutation,but this known genetic factors can only explain a small part of the case,and many unknown genetic factors need to be further clarified.Spermatogenesis is the process of spermatogenesis from spermatogonial stem cells into highly differentiated sperm cells,which is regulated by many genes,any of which may affect the normal spermatogenesis,leading to spermatogenic failure.Therefore,these genes are also seen as important candidate genes affecting male infertility.The study on the genetic etiology and pathogenesis of male infertility has important significance in the study of the genetic etiology and pathogenesis of male infertility.P73 gene is an important member of the p53 gene family,it has certain similarity with the p53 gene in structure and function,and the loss or abnormality of p73 transcription activity is related to cell cycle and apoptosis,and p73 gene splicing can inhibit cell growth,p73 over-expression can promote cell death.In recent years,p73 gene is related to the cause of esophageal cancer,gastric cancer and cervical cancer.In reproductive function,the integrity of germ cell genome,embryo implantation and endocrine are very important,especially in the development of sperm and neurons play an important role.Studies in mice show that defect gene of P73 can lead to spermatogenic failure and male infertility,suggesting that p73 gene plays an important role in sperm growth,its variation may be related to spermatogenic dysfunction and male infertility.EPSTI1,a Interferon response gene,is initially isolated from human breast fibroblasts through three-dimensional co-culture,and has been identified as a inducible gene of human breast cancer cells.The expression level of EPSTI1 is related to tumorigenesis and migration,stem cell-like,epithelial-mesenchymal transition(EMT)and invasion and metastasis of breast cancer.Subsequently,studies have shown that the expression of EPSTI1 gene is related to cell apoptosis.The expression of EPSTI1 gene in male testis is also high.GWAS analysis suggests that SNP may be associated with spermatogenic failure,and is also considered as an important candidate gene for male infertility,but whether it is related to male infertility is susceptible to further study.At present,due to the lack of information about the effect of P73 gene on male infertility and spermatogenic dysfunction both domestic and overseas.In addition,the study of EPSTI1 gene and spermatogenic dysfunction is less.In view of this,this study uses the polymerase chain reaction(PCR),restriction fragment length polymorphism(PCR),restriction fragment length polymorphism(RFLP)and DNA sequencing to investigate the relationship between p73 gene and EPSTI1 gene in SNP rs12870438,rs61389340 and rs1044856 locus with spermatogenic dysfunction in the future.The results are as follows:By comparing the frequency and genotype frequency of P73 gene in case group and normal control group,allele at frequency(28.9 %vs.22.4,P = 0.017,OR = 1.41,95 % CI = 1.07-1.85)significantly decreased(48.5 % vs.59.1,P = 0.048,OR = 0.65,95 % CI = 0.46-0.91).Comparing the case analysis of EPSTI1 gene,the results of three SNP sites of EPSTI1 gene are as follows:(1)The polymorphism were not observed in SNP rs1389340 locus;(2)In SNP rs1044856 locus,the frequency distribution of TA genotype didn’t have significant difference,and didn’t relate to male infertility;(3)SNP rs12870438 allele frequency A in patient group(24.4 %vs17.2%,P = 0.020,OR=0.433,95%CI=0.303-0.621)was significantly higher than the control group,and the genotype GG was significantly lower(53.7%vs69.2%,P=0.007,OR=1.563,95%CI=1.070-2.285).These results suggest that the polymorphism G4C14-to-A4T14 in p73 gene may be related to serious spermatogenic dysfunction;the polymorphism of EPSTI1 gene in SNP rs12870438 locus may be related to oligozoospermia.