Polymorphisms of estrogen-related genes jointly confer susceptibility to human spermatogenic defect.
OBJECTIVE
To establish a multilocus model for studying the effect of estrogen-related genes on impaired spermatogenesis.


METHODS
Prospective study.


METHODS
University-based reproductive clinics and genetics laboratory.


METHODS
A total of 183 oligozoospermatic (sperm count <20 x 10(6)/mL) or azoospermatic males and 120 fertile control males were included.


METHODS
A total of 16 single nucleotide polymorphisms (SNPs) from nine genes (estrogen receptors [ER-alpha, ER-beta], estrogen synthesizing/metabolizing genes [CYP17, CYP19A1, HSD17B2, CYP1A1, CYP1B1, COMT], and transport genes [SHBG]) were genotyped. The combinatorial effect of multiple genetic variants was assessed using the multilocus model.


METHODS
Significantly associated SNPs and odds ratio (OR).


RESULTS
Six SNPs from five genes (rs180113 of ER-alpha gene, rs1256049 of ER-beta gene, rs1048943 of CYP1A1 gene, rs8191246 of HSD17B2 gene, and rs1799941 along with rs6259 of SHBG gene) were found to be significantly associated with spermatogenic defect. The genes were further divided into three categories according to their functions (receptors, synthesis and metabolism, and transporter). Based on our multilocus risk model, men with risk alleles in two of the three gene families had increased risk of impaired sperm production (OR = 10.5). The OR further increased to 34.6 for men with unfavorable alleles for all three gene families.


CONCLUSIONS
Polymorphisms of estrogen-related genes jointly confer susceptibility to human spermatogenic defect at the prereceptor, receptor, and postreceptor levels in the Taiwanese Han population.
Su
Mei-Tsz
MT
Departments of Obstetrics and Gynecology, National Cheng Kung University College of Medicine, Tainan City, Taiwan, Republic of China.
Chen
Chien-Hsiun
CH
Kuo
Po-Hsiu
PH
Hsu
Chao-Chin
CC
Lee
I-Wen
IW
Pan
Hisan-An
HA
Chen
Ying-Ting
YT
Kuo
Pao-Lin
PL
D000328:Adult; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D004960:Estradiol Dehydrogenases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007527:Isoenzymes; D016015:Logistic Models; D008297:Male; D008957:Models, Genetic; D016017:Odds Ratio; D009845:Oligospermia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013624:Taiwan; D055815:Young Adult
D004798:Enzymes; D007527:Isoenzymes; D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin; D003577:Cytochrome P-450 Enzyme System; D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human; D002394:Catechol O-Methyltransferase