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

The Human 8-oxoG DNA Glycosylase 1 (OGG1) Ser 326 Cys Polymorphism in Infertile Men

César Antonio González-Díaz  1 , María Antonieta Suárez-Souto  1 , Elvia Pérez-Soto  2 , Modesto Gómez-López  1 , Jacobo Esteban Munguía-Cervantes  3 , Nadia Mabel Pérez-Vielma  4 , Virginia Sánchez-Monroy  1
Affiliations

The Human 8-oxoG DNA Glycosylase 1 (OGG1) Ser 326 Cys Polymorphism in Infertile Men

César Antonio González-Díaz et al. Biomedicines. .

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 Ser326Cys have demonstrated that the Cys326Cys genotype could be the cause of an increment in oxidative DNA damage. In this study, the OGG1 Ser326Cys 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 Cys (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 Cys (G) allele carrier could be a factor associated with American infertile populations. The values of 8-OHdG were twofold higher in carriers of the Cys326Cys (GG) genotype than the other genotypes and, in concordance, the TAC levels were threefold lower in Cys326Cys (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 Cys326Cys (GG) genotype is associated with oxidative DNA damage that could contribute to male infertility.

Keywords: 8-oxoguanine DNA glycosylase 1; infertility; semen.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
OGG1 Ser326Cys polymorphism detection. (A) Agarose (2%) gel electrophoresis of amplicons from representative samples. Lane 1: DNA ladder 100 pb. Lanes 2–8: 300 pb amplicons of OGG1 obtained from representative samples. (B) Representative electropherograms showing the sequence of OGG1 amplicons with genotypes detected.
Figure 2
Figure 2
8-Hydroxi-2′deoxyguanosine (8-OHdG) levels by genotype. Data are expressed as mean ± standard deviation and were analyzed using one-way ANOVA. * Genotype GG vs. other genotype groups shows significant difference (significant difference is defined as p ≤ 0.05) and a large effect size (η2p = 0.184).
Figure 3
Figure 3
Total antioxidant capacity (TAC) levels by genotype. Data are expressed as median and compared using Kruskal–Wallis test. * Genotype GG vs. other genotype groups shows significant difference. Significant difference is defined as p ≤ 0.05 and a large effect size (η2p = 0.102).
Figure 4
Figure 4
EBiS magnitude spectra for representative samples with the Cys326Cys (GG), Ser326Ser (CC), and Ser326Cys (CG) genotypes. The levels of 8-OHdG are indicated by genotype in pg/mL.
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