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  • Title: Polymorphisms of estrogen-related genes jointly confer susceptibility to human spermatogenic defect.
    Author: Su MT, Chen CH, Kuo PH, Hsu CC, Lee IW, Pan HA, Chen YT, Kuo PL.
    Journal: Fertil Steril; 2010 Jan; 93(1):141-9. PubMed ID: 18980759.
    Abstract:
    OBJECTIVE: To establish a multilocus model for studying the effect of estrogen-related genes on impaired spermatogenesis. DESIGN: Prospective study. SETTING: University-based reproductive clinics and genetics laboratory. PATIENT(S): A total of 183 oligozoospermatic (sperm count <20 x 10(6)/mL) or azoospermatic males and 120 fertile control males were included. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): Significantly associated SNPs and odds ratio (OR). RESULT(S): 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. CONCLUSION(S): Polymorphisms of estrogen-related genes jointly confer susceptibility to human spermatogenic defect at the prereceptor, receptor, and postreceptor levels in the Taiwanese Han population.
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