The stromal antigen 3(STAG3)gene,encoding a meiosis-specific cohesin component,is a strong candidate for causing male infertility,but little is known about this gene so far.We identified STAG3 in patients with nonobst...The stromal antigen 3(STAG3)gene,encoding a meiosis-specific cohesin component,is a strong candidate for causing male infertility,but little is known about this gene so far.We identified STAG3 in patients with nonobstructive azoospermia(NOA)and normozoospermia in the Korean population.The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis.A total of 30 sequence variations were identified in this study.Of the total,seven were exonic variants,18 were intronic variants,one was in the 5’-UTR,and four were in the 3'-UTR.Pathogenic variations that directly caused NOA were not identified.However,two variants,c.3669+35C>G(rs1727130)and+198A>T(rs1052482),showed significant differences in the frequency between the patient and control groups(P=0.021,odds ratio[OR]:1.79,95%confidence interval[Cl]:1.098-2.918)and were tightly linked in the linkage disequilibrium(LD)block.When pmir-rs1052482A was cotransfected with miR-3162-5p,there was a substantial decrease in luciferase activity,compared with pmir-rs1052482T.This result suggests that rsl052482 was located within a binding site of miR-3162-5p in the STAG33'-UTR,and the minor allele,the rs1052482T polymorphism,might offset inhibition by miR-3162-5p.We are the first to identify a total of 30 single-nucleotide variations(SNVs)of STAG3 gene in the Korean population.We found that two SNVs(rs1727130 and rsl052482)located in the 3'-UTR region may be associated with the NOA phenotype.Our findings contribute to understanding male infertility with spermatogenic impairment.展开更多
基金This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(Grant No.H14C0106020014).
文摘The stromal antigen 3(STAG3)gene,encoding a meiosis-specific cohesin component,is a strong candidate for causing male infertility,but little is known about this gene so far.We identified STAG3 in patients with nonobstructive azoospermia(NOA)and normozoospermia in the Korean population.The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis.A total of 30 sequence variations were identified in this study.Of the total,seven were exonic variants,18 were intronic variants,one was in the 5’-UTR,and four were in the 3'-UTR.Pathogenic variations that directly caused NOA were not identified.However,two variants,c.3669+35C>G(rs1727130)and+198A>T(rs1052482),showed significant differences in the frequency between the patient and control groups(P=0.021,odds ratio[OR]:1.79,95%confidence interval[Cl]:1.098-2.918)and were tightly linked in the linkage disequilibrium(LD)block.When pmir-rs1052482A was cotransfected with miR-3162-5p,there was a substantial decrease in luciferase activity,compared with pmir-rs1052482T.This result suggests that rsl052482 was located within a binding site of miR-3162-5p in the STAG33'-UTR,and the minor allele,the rs1052482T polymorphism,might offset inhibition by miR-3162-5p.We are the first to identify a total of 30 single-nucleotide variations(SNVs)of STAG3 gene in the Korean population.We found that two SNVs(rs1727130 and rsl052482)located in the 3'-UTR region may be associated with the NOA phenotype.Our findings contribute to understanding male infertility with spermatogenic impairment.
