Ala16Val SOD2 polymorphism is associated with higher pregnancy rates in in vitro fertilization cycles

Ruiz-Sanz, José Ignacio; Aurrekoetxea, Igor; Matorras, Roberto; Ruiz‐Larrea, M. Begoña

doi:10.1016/j.fertnstert.2010.11.022

Cited by 25 publications

(15 citation statements)

References 38 publications

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“…These results are in consonance with previous studies describing the toxicogenetic and pharmacogenetic effects of the Ala16Val-SOD2 SNP on PBMCs exposed to xenobiotic molecules [21] , [22] . Another important effect observed in this study was the MTX effect on cytokines involved in the inflammatory response, but this result seems to not be influenced by SOD2 metabolism.…”

Section: Discussionsupporting

confidence: 92%

“…To obtain PBMCs, the blood samples were first collected by venipuncture from 120 healthy adult subjects (26.4±7.3 years old) living in a Brazilian region (Rio Grande do Sul) without a history of diseases that are treated with MTX, non-smokers, not obese, no use of chronic medication or vitamin supplements, no previous cardiovascular medical history or hypertensive disorder, and no metabolic diseases or other morbidity that could affect the results. The Ala16Val-SOD2 genotyping was determined by polymerase chain reaction using a direct total blood cell sample and Tetra-Primer ARMS-PCR assay as described by Ruiz-Sanz et al [22] with slight modifications. Briefly, two primer pairs were used to amplify and determined the genotype of a DNA fragment containing the Ala16Val SNP in the human SOD2 sequence.…”

Section: Methodsmentioning

confidence: 99%

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Methotrexate-Related Response on Human Peripheral Blood Mononuclear Cells May Be Modulated by the Ala16Val-SOD2 Gene Polymorphism

et al. 2014

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Methotrexate (MTX) is a folic acid antagonist used in high doses as an anti-cancer treatment and in low doses for the treatment of some autoimmune diseases. MTX use has been linked to oxidative imbalance, which may cause multi-organ toxicities that can be attenuated by antioxidant supplementation. Despite the oxidative effect of MTX, the influence of antioxidant gene polymorphisms on MTX toxicity is not well studied. Therefore, we analyzed here whether a genetic imbalance of the manganese-dependent superoxide dismutase (SOD2) gene could have some impact on the MTX cytotoxic response. An in vitro study using human peripheral blood mononuclear cells (PBMCs) obtained from carriers with different Ala16Val-SOD2 genotypes (AA, VV and AV) was carried out, and the effect on cell viability and proliferation was analyzed, as well as the effect on oxidative, inflammatory and apoptotic markers. AA-PBMCs that present higher SOD2 efficiencies were more resistance to high MTX doses (10 and 100 µM) than were the VV and AV genotypes. Both lipoperoxidation and ROS levels increased significantly in PBMCs exposed to MTX independent of Ala16Val-SOD2 genotypes, whereas increased protein carbonylation was observed only in PBMCs from V allele carriers. The AA-PBMCs exposed to MTX showed decreasing SOD2 activity, but a concomitant up regulation of the SOD2 gene was observed. A significant increase in glutathione peroxidase (GPX) levels was observed in all PBMCs exposed to MTX. However, this effect was more intense in AA-PBMCs. Caspase-8 and -3 levels were increased in cells exposed to MTX, but the modulation of these genes, as well as that of the Bax and Bcl-2 genes involved in the apoptosis pathway, presented a modulation that was dependent on the SOD2 genotype. MTX at a concentration of 10 µM also increased inflammatory cytokines (IL-1β, IL-6, TNFα and Igγ) and decreased the level of IL-10 anti-inflammatory cytokine, independent of SOD2 genetic background. The results suggest that potential pharmacogenetic effect on the cytotoxic response to MTX due differential redox status of cells carriers different SOD2 genotypes.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Methotrexate-Related Response on Human Peripheral Blood Mononuclear Cells May Be Modulated by the Ala16Val-SOD2 Gene Polymorphism

et al. 2014

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“…Genetic variations in SOD may also be related to reproductive outcomes. The Ala16Val polymorphism in the SOD2 gene is associated with infertility and pregnancy rate in IVF cycles [ 39 ]. In a case-control study, the presence of the Ala- MnSOD allele (rs4880) was associated with a significant increase in the risk of infertility in male subjects [ 40 ].…”

Section: Genetic Variations In Antioxidant Genes Associated With Mmentioning

confidence: 99%

Variations in Antioxidant Genes and Male Infertility

Huang

2015

BioMed Research International

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Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted.

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“…A valine at position 16 produces a conformational change in the protein structure, which may decrease efficiency. Interestingly, the AA geno type was associated with higher number of total oocytes following COS [59]. Larger population studies are needed to validate this finding.…”

Section: Sod2mentioning

confidence: 91%

Pharmacogenetics of Ovarian Response

et al. 2014

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Effective controlled ovarian stimulation (COS) is crucial for IVF outcome. Ovarian response to follicle-stimulating hormone, however, varies widely among women undergoing ovarian stimulation. Advance identification of patients who will elicit a poor or high response to standard treatment would be of great clinical benefit for such patients. Application of pharmacogenetics to ovarian response may predict stimulation success but also help in the adjustment and design of doses prior to treatment. Different studies have examined the impact of variations in follicle-stimulating hormone receptor, biochemical pathways involved in estrogen production and action, folliculogenesis and other aspects. Recently, gene-association studies have tried to identify a number of genetic variations affecting interindividual variability in COS.

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Ala16Val SOD2 polymorphism is associated with higher pregnancy rates in in vitro fertilization cycles

Cited by 25 publications

References 38 publications

Methotrexate-Related Response on Human Peripheral Blood Mononuclear Cells May Be Modulated by the Ala16Val-SOD2 Gene Polymorphism

Methotrexate-Related Response on Human Peripheral Blood Mononuclear Cells May Be Modulated by the Ala16Val-SOD2 Gene Polymorphism

Variations in Antioxidant Genes and Male Infertility

Pharmacogenetics of Ovarian Response

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