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不育男性中人类8-氧代鸟嘌呤DNA糖基化酶1()326多态性

The Human 8-oxoG DNA Glycosylase 1 () 326 Polymorphism in Infertile Men.

作者信息

González-Díaz César Antonio, Suárez-Souto María Antonieta, Pérez-Soto Elvia, Gómez-López Modesto, Munguía-Cervantes Jacobo Esteban, Pérez-Vielma Nadia Mabel, Sánchez-Monroy Virginia

机构信息

Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico.

Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Mexico City 07320, Mexico.

出版信息

Biomedicines. 2024 Oct 9;12(10):2286. doi: 10.3390/biomedicines12102286.

Abstract

BACKGROUND/OBJECTIVES: 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a form of oxidative DNA damage caused by oxidative stress (OS), which is considered a major factor in male infertility. The cellular defense system against 8-OHdG involves base excision repair (BER) with the enzyme 8-Oxoguanine DNA glycosylase 1 (OGG1). However, studies on the single-nucleotide polymorphism (SNP) OGG1 326 have demonstrated that the 326 genotype could be the cause of an increment in oxidative DNA damage. In this study, the OGG1 326 polymorphism and its effect on DNA oxidation were evaluated in 118 infertile men.

METHODS

Polymorphic screening was performed using TaqMan allelic discrimination assays, and oxidative DNA damage was evaluated through the quantification of 8-OHdG and total antioxidant capacity (TAC); in addition, electrical bioimpedance spectroscopy (EBiS) measurements were used as a reference for different electrical properties associated with 8-OHdG concentrations.

RESULTS

The detected (G) allele frequency (0.4) was higher compared to the allele frequency reported in the "Allele Frequency Aggregator" (ALFA) and "Haplotype Map" (HapMap) projects for American populations (0.21-0.29), suggesting that the (G) allele carrier could be a factor associated with American infertile populations. The values of 8-OHdG were twofold higher in carriers of the 326 (GG) genotype than the other genotypes and, in concordance, the TAC levels were threefold lower in 326 (GG) genotype carriers compared to the other genotypes. Moreover, the EBiS magnitude exhibited potential for the detection of different oxidative damage in DNA samples between genotypes.

CONCLUSIONS

The 326 (GG) genotype is associated with oxidative DNA damage that could contribute to male infertility.

摘要

背景/目的:8-羟基-2'-脱氧鸟苷(8-OHdG)是氧化应激(OS)导致的一种氧化性DNA损伤形式,氧化应激被认为是男性不育的主要因素。针对8-OHdG的细胞防御系统涉及由8-氧鸟嘌呤DNA糖基化酶1(OGG1)进行的碱基切除修复(BER)。然而,关于单核苷酸多态性(SNP)OGG1 326的研究表明,326基因型可能是氧化性DNA损伤增加的原因。在本研究中,对118名不育男性的OGG1 326多态性及其对DNA氧化的影响进行了评估。

方法

使用TaqMan等位基因鉴别分析进行多态性筛查,并通过对8-OHdG和总抗氧化能力(TAC)的定量评估氧化性DNA损伤;此外,电阻抗光谱(EBiS)测量用作与8-OHdG浓度相关的不同电学性质的参考。

结果

检测到的(G)等位基因频率(0.4)高于“等位基因频率汇总器”(ALFA)和“单倍型图谱”(HapMap)项目中报道的美国人群的等位基因频率(0.21 - 0.29),这表明(G)等位基因携带者可能是与美国不育人群相关的一个因素。326(GG)基因型携带者的8-OHdG值比其他基因型高两倍,与此一致,326(GG)基因型携带者的TAC水平比其他基因型低三倍。此外,EBiS幅度显示出检测不同基因型DNA样本中氧化性损伤的潜力。

结论

326(GG)基因型与可能导致男性不育的氧化性DNA损伤相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5c/11505341/aad44f8bf843/biomedicines-12-02286-g001.jpg

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