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NFKB1基因rs28362491和前体微小RNA-146a基因rs2910164单核苷酸多态性对特发性少精子症患者E-钙黏蛋白表达的影响:一项病例对照研究

NFKB1 rs28362491 and pre-miRNA-146a rs2910164 SNPs on E-Cadherin expression in case of idiopathic oligospermia: A case-control study.

作者信息

Tunçdemir Matem, Yenmiş Güven, Tombultürk Kübra, Arkan Hülya, Soydaş Tuğba, Burak Tek Rasit, Altıntaş Özlem, Özkara Hamdi, Kanıgür-Sultuybek Gönül

机构信息

Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

Acıbadem Healthcare Services, Acıbadem LABGEN Genetic Diagnostic Center, Acibadem University Kerem Aydınlar Campus, Icerenkoy Kayisdagi Istanbul, Turkey.

出版信息

Int J Reprod Biomed. 2018 Apr;16(4):247-254.

Abstract

BACKGROUND

A notable proportion of idiopathic male infertility cases is accompanied by oligozoospermia; and yet, the molecular mechanisms of fertilization problem underlying this defect are still unclear. Epithelial cadherin has been involved in several calcium-dependent cell-to-cell adhesion events; however, its participation in gamete interaction has also not been fully investigated.

OBJECTIVE

The aim was to investigate the changes in the expression of E-cadherin, based on the frequency of Single nucleotide polymorphisms in Nuclear Factor Kappa-B 1 and pre-mir-146a in oligospermic men.

MATERIALS AND METHODS

In this case-control study, semen and blood samples of 131 oligospermic men as the case group and 239 fertile healthy men as the control group were analyzed. Variants single nucleotide polymorphisms rs28362491 and rs2910164 were performed using polymerase chain reaction-restriction fragment length polymorphism method and E-cadherin expression were determined by immunoprecipitation studies.

RESULTS

ins/ins genotype of rs28362491 was determined as a risk factor for idiopathic oligospermia by 1.73 times (p=0.0218), whereas no significant differences were found between the groups concerning pre-mir-146a rs2910164 polymorphism (p=0.2274 in case of GC genotype and p=0.9052 in case of GG genotype). Combined genotype analysis results did not show any notable differences between the multiple comparisons of 28362491-rs2910164 in oligospermic men and control groups. In addition, E-cadherin expression of oligospermic men with ins/ins genotype was significantly lower than patients with del/ins genotype (p=0.0221). E-cadherin expression level was low in oligospermic men with respect to the control group in presence of ins/ins genotype of NFKB1 gene.

CONCLUSION

These results suggest that ins allele prevents binding of surface proteins to spermatozoa, leading to a low affinity of sperm-oocyte interaction in oligospermic men.

摘要

背景

相当一部分特发性男性不育病例伴有少精子症;然而,这种缺陷背后受精问题的分子机制仍不清楚。上皮钙黏蛋白参与了多种钙依赖性细胞间黏附事件;然而,其在配子相互作用中的作用也尚未得到充分研究。

目的

基于少精子症男性中核因子κB 1和前体微小RNA-146a单核苷酸多态性的频率,研究E-钙黏蛋白表达的变化。

材料与方法

在这项病例对照研究中,分析了131例少精子症男性作为病例组的精液和血液样本,以及239例生育健康男性作为对照组的样本。采用聚合酶链反应-限制性片段长度多态性方法检测单核苷酸多态性rs28362491和rs2910164的变异,并通过免疫沉淀研究测定E-钙黏蛋白的表达。

结果

rs28362491的ins/ins基因型被确定为特发性少精子症的危险因素,风险倍数为1.73倍(p = 0.0218),而两组之间在前体微小RNA-146a rs2910164多态性方面未发现显著差异(GC基因型时p = 0.2274,GG基因型时p = 0.9052)。联合基因型分析结果显示,少精子症男性和对照组在28362491-rs2910164的多重比较之间没有任何显著差异。此外,ins/ins基因型的少精子症男性的E-钙黏蛋白表达明显低于del/ins基因型的患者(p = 0.0221)。在存在NFKB1基因ins/ins基因型的情况下,少精子症男性的E-钙黏蛋白表达水平相对于对照组较低。

结论

这些结果表明,ins等位基因阻止表面蛋白与精子结合,导致少精子症男性精子-卵母细胞相互作用的亲和力降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2202/6004596/ba72032eada7/ijrb-16-247-g001.jpg

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