New candidate genes associated to endometriosis

Abstract

A previous GWAS study performed on Brazilian pooled samples indicated some SNPs (single nucleotide polymorphisms) differentially frequent in infertile patients with endometriosis and controls. Some of them were located in the genes whose biological function suggests that they could be associated with endometriosis pathogenesis; thus, the purpose here was to confirm GWAS findings in a larger group of cases and controls in order to associate the results with the pathogenesis of endometriosis. Then, a genetic association study comprising 394 infertile women with endometriosis and 650 fertile control women was conducted. TaqMan allelic discrimination assays were used to investigate the frequency of three SNPs in the genes KAZN (rs10928050), LAMA5 (rs2427284), and TAC3 (rs733629). The analysis revealed a significant association of KAZN rs10928050 (p = .015) and LAMA5 rs2427284 (p = .0059) SNPs with endometriosis-related infertility, while TAC3 rs733629 showed no difference between cases and controls. As a conclusion, it was possible to observe that individual genotyping of a larger sample of patients and controls confirmed the association among KAZN and LAMA5 with endometriosis-related infertility and revealed new candidate genes contributing to the condition.

摘要

之前在巴西进行的一项全基因组关联分析研究（GWAS）显示, 一些单核苷酸多态性(SNPs) 在不孕的子宫内膜异位症患者和正常对照组人群中存在有差异。这些片段所具有的生物功能提示这些基因片段可能与子宫内膜异位症的发病相关。本研究的目的是在更大样本的病例对照研究中证实GWAS的发现, 以便将其结果与子宫内膜异位症的发病机制联系起来。本研究将394名子宫内膜异位症合并不孕的女性和650名具有正常生育力的女性进行了基因相关性研究。采用TaqMan等位基因判别法对以下三个基因：KAZN (rs10928050), LAMA5 (rs2427284)以及 TAC3 (rs733629)中3个单核苷酸多态性出现的频率进行了研究。结果显示：KAZN rs10928050 (p=.015) 和 LAMA5 rs2427284 (p=.0059)与子宫内膜异位症患者的不孕症相关, 但是TAC3 rs733629出现的频率在两组人群中并没有差异。综上所述, 在更大样本的关于个体基因分型病例对照研究中我们可以观察到：KAZN和LAMA5与子宫内膜症的不孕相关, 并发现了导致这种情况的新候选基因。

Keywords:

• Molecular biomarker
• polymorphism
• infertility
• endometriosis
• genotyping

Acknowledgements

Authors would like to thank all patients and controls that kindly voluntary to participate in the study.

Disclosure statement

The authors disclose no conflict of interest.

Additional information

Funding

This work was supported by FAPESP (Fundo de Amparo à pesquisa do Estado de São Paulo) under Grant number 2011/01363–7; FAPESP under Scholarships 2012/22394–8 and 2014/07136–8 for Fernanda Mafra; and CNPq (Conselho Nacional de desenvolvimento científico e tecnológico) under Scholarship for Michelle Catto.