title: Quantitative trait analysis suggests polymorphisms of estrogen-related genes regulate human sperm concentrations and motility.
abstract: BACKGROUND
  Human spermatogenesis is regulated by complex networks, and estrogens are recognized as one of the significant regulators of spermatogenesis. We tested the associations between variants of estrogen-related genes and semen parameters.
  
  
  METHODS
  We performed genotyping for genetic variants of estrogen-related genes and quantitative trait analysis of fertile and infertile men with well-characterized reproductive phenotypes. Men with known semen parameters (n= 677) were enrolled, including 210 fertile men and 467 infertile men. A total of 17 genetic markers from 10 genes, including 2 estrogen receptors (ER-α, ER-β), 7 estrogen synthesizing/metabolizing genes (CYP19A1, HSD17B1, CYP1A1, CYP1B1, COMT, GSTM1, GSTT1) and 1 transport gene (SHBG) were genotyped. Sperm concentration, motility and morphology were taken as quantitative traits to correlate with genetic variants in the estrogen-related genes.
  
  
  RESULTS
  Five genes (rs1801132 and rs2228480 of the ER-α gene, rs1256049 and rs4986938 of the ER-β gene, rs605059 of the HSD17B1 gene, rs1799941 of the SHBG gene and rs1048943 and rs4646903 of the CYP1A1 gene) were found to be significantly associated with sperm concentration (P< 0.01), while five genes (rs1801132 of the ER-a gene, rs1256049 of the ER-β gene, rs1048943 of the CYP1A1 gene, rs605059 of the HSD17B1 gene and rs1799941 along with rs6259 of the SHBG gene) were associated with sperm motility (P< 0.01). None of the estrogen-related genes were associated with sperm morphology. With an increasing number of risk alleles, sperm concentration and motility tended to deteriorate and show a loci-dosage effect.
  
  
  CONCLUSIONS
  Quantitative trait analysis based on a limited number of genetic markers suggests that estrogen-related genes mainly regulate sperm concentration and motility.
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Lee
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
authors.forename: Mei-Tsz
authors.initials: MT
authors.lastname: Su
authors.forename: Long-Ching
authors.initials: LC
authors.lastname: Kuan
authors.forename: Chao-Chin
authors.initials: CC
authors.lastname: Hsu
authors.forename: Pao-Lin
authors.initials: PL
authors.lastname: Kuo
mesh_terms: D004967:Estrogens / Q000235:genetics / Q000502:physiology*; D005298:Fertility / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D013076:Sperm Count; D013081:Sperm Motility / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics
chemical_list: D004967:Estrogens