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Zhao H.,Shandong University | Zhao H.,National Research Center for Assisted Reproductive Technology | Zhao H.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Zhao H.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 5 more authors.
Molecular Human Reproduction | Year: 2013

Many genetic association studies have been performed to investigate disorders of female reproduction, such as polycystic ovary syndrome, premature ovarian failure and endometriosis. These disorders typically manifest heterogeneously, and their pathogeneses are influenced by polygenic and environmental factors. Researchers evaluating these genetic associations have chosen candidate genes related to hormone action, steroid biosynthesis, inflammatory cytokines and autoimmune factors. Several of these genes have yielded statistically significant associations with female reproductive disorders; however, few associations have been robust and reproducible. Whole-genome association studies generate more reliable and unbiased results and represent a breakthrough in genetic studies of female reproduction. Nevertheless, to date only a very small fraction of the overall heritability has been identified and so further studies are needed. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Li T.,Shandong University | Li T.,National Research Center for Assisted Reproductive Technology | Li T.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Li T.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 29 more authors.
Journal of Medical Genetics | Year: 2012

Background: A previously reported genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in Han Chinese found that several loci of p value around 10e-5 warrant investigation. Replication of the GWAS was applied in this study to determine whether gene YAP1 (yeast associated protein 1) is associated with PCOS. Methods: An independent set of 1115 PCOS patients and 1137 controls were recruited; single nucleotide polymorphisms (SNPs) rs11225138, rs11225161, and rs11225166 from YAP1 were selected for the replication study. Real-time quantitative PCR was applied for genotyping by TaqMan-MGB probe assay. Results: Meta-analysis showed that the allele frequency of rs11225161 (A/G) was significantly different between PCOS and controls at a GWA significance (Pmeta =3.98e 09). Genotype-phenotype correlation study found 30 min and 60 min glucose of the oral glucose tolerance test were higher in PCOS patients with rs11225161 risk allele A. The G allele of SNP rs11225138 (G/C) was a further risk factor for higher luteinising hormone level in PCOS patients (p=0.041). Conclusion: YAP1 appears to be a new susceptibility gene for PCOS in Han Chinese women.

Guo T.,Shandong University | Guo T.,National Research Center for Assisted Reproductive Technology | Guo T.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Qin Y.,Shandong University | And 17 more authors.
International Journal of Andrology | Year: 2012

Chromosomal polymorphism has been reported to be associated with infertility, but its effect on IVF/ICSI-ET outcome is still controversial. To evaluate whether or not chromosomal polymorphism in men plays a role in spermatogenesis and the outcome of IVF/ICSI-ET, we retrospectively analysed 281 infertile couples. Measures included fertilization rate, implantation rate, pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate and preterm rate. Men with chromosomal polymorphism had significantly higher frequencies of severe oligozoospermia and azoospermia than those without (37.12% vs. 16.11%, p<0.001; 27.27% vs. 10.74%, p<0.001; respectively). Significantly, lower fertilization rate (68.02% vs. 78.00%, p<0.001) and clinical pregnancy rate (45.00% vs. 66.67%, p=0.031) were observed in polymorphism-carrying men with severe oligozoospermia compared with non-carriers with severe oligozoospermia. This suggests that chromosomal polymorphism has adverse effects on spermatogenesis, negatively influencing the outcome of IVF/ICSI-ET treatment. Polymorphic variations on the Y chromosome have been found to be the most prevalent polymorphism in infertile men, most frequently occurring in patients with severe oligozoospermia. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

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