title: Strong association ofSLC1A1andDPF3gene variants with idiopathic male infertility in Han Chinese.
abstract: Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. In recent years, several genome-wide single-nucleotide polymorphism (SNP) association studies (GWAS) have been performed on azoospermia and/or oligozoospermia in different populations including two GWAS on nonobstructive azoospermia in China; however, the association of SNPs with idiopathic male infertility, especially asthenozoospermia and oligozoospermia, and their correlation with semen parameters are still not clear. To investigate genetic variants associated with idiopathic male infertility (asthenozoospermia, oligozoospermia, and oligoasthenozoospermia) in Chinese Han people, 20 candidate SNPs were selected from GWAS results and genotyped using the Sequenom MassARRAY assay. A total of 136 subfertile men and 456 healthy fertile men were recruited. rs6476866 in SLC1A1 (P = 1.919E-4, OR = 0.5905, 95% CI: 0.447-0.78) and rs10129954 in DPF3 (P = 0.0023, OR = 2.199, 95% CI: 1.311-3.689) were strongly associated with idiopathic male infertility. In addition, positive associations were observed between asthenozoospermia and rs215702 in LSM5 (P = 0.0016, OR = 1.479, 95% CI: 1.075-2.033) and between oligoasthenozoospermia and rs2477686 in PEX10 (P = 0.0011, OR = 2.935, 95% CI: 1.492-5.775). In addition, six SNPs (rs215702 in LSM5, rs6476866 in SLC1A1, rs10129954 in DPF3, rs1801133 in MTHFR, rs2477686 in PEX10, and rs10841496 in PED3A) were significantly correlated with semen quality alterations. Our results suggest that idiopathic male infertility in different ethnic groups may share the same mechanism or pathway. Cohort expansion and further mechanistic studies on the role of genetic factors that influence spermatogenesis and sperm progressive motility are suggested.
authors.affiliation: Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Reproductive Medical Research Centre, People's Hospital of Shiyan, Shiyan 442000, China.
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Zhang
authors.affiliation: Reproductive Medical Research Centre, People's Hospital of Shiyan, Shiyan 442000, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Peng
authors.affiliation: Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Lin
authors.affiliation: Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Huang
authors.affiliation: Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Chu
authors.affiliation: Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
authors.forename: Zhao-Qing
authors.initials: ZQ
authors.lastname: Yang
mesh_terms: D000328:Adult; D044466:Asian People; D053627:Asthenozoospermia / Q000453:epidemiology / Q000235:genetics; D053713:Azoospermia; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012661:Semen; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C452161:DPF3 protein, human; D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human; D014157:Transcription Factors