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Prevalence of mitochondrial superoxide dismutase gene Ala16Val polymorphism among Caucasian and Mongoloid adolescents
Free Radical Biology and Medicine 128 (2018) S136–S141
Contents lists available at ScienceDirect
Free Radical Biology and Medicine journal homepage: www.elsevier.com/locate/freeradbiomed
Genetics/Epigenetics
328 329
Prevalence of mitochondrial superoxide dismutase gene Ala16Val polymorphism among Caucasian and Mongoloid adolescents Tatjana A. Bairova*, Oksana A. Ershova, Marina Darenskaya, Lyubov Kolesnikova Scientific Centre for Family Health and Human Reproduction Problems, Russian Federation, Russian Federation
Background: Mitochondrial superoxide dismutase (SOD2) catalyzes the superoxide dismutation into oxygen and hydrogen peroxide. The activity of SOD2 is determined by the SOD2 gene. The SOD2 gene is located on the chromosome 6q25.3. One of the most studied polymorphisms of this gene is polymorphism Ala16Val, which replaces the amino acid alanine with valine in the 16 position of the amino acid sequence. As a result, the alpha-helix of the SOD2 protein is disrupted. The altered protein has a 3040% activity decrease, increasing the susceptibility of the cell to oxidative stress. The prevalence of Val allele of Ala16Val polymorphism varies in different races: 12.5% in Mongoloids, 46.6% in Caucasians. Methods: We examined 119 adolescents aged 14-17 years: 65 Caucasian teenagers (Russians, average age 15.02 7 0.98 years) and 54 Mongoloid teenagers (Buryats, mean age 15.31 7 0.96 years). Genomic DNA was extracted from whole blood by commercial kits. Ala16Val polymorphism was genotyped using a polymerase chain reaction with electrophoresis detection. Results: In the group of Caucasian adolescents, the frequencies of the genotypes Ala / Ala, Ala / Val and Val / Val are 27.7%; 43.1% and 29.2%. The frequency of Val allele is 50.8%. Among Buryats, the genotypes Ala / Ala, Ala / Val and Val / Val were detected in 7.4%; 53.7% and 38.9%, allele Val in 65.7%. This distribution of genotypes frequencies corresponds to the Hardy-Weinberg Law in both samples. Conclusion: Allele Val of Ala16Val polymorphism of superoxide dismutase 2 gene in the group of Buryat adolescents occurs more often than in the group of Russian adolescents (χ² ¼ 4.82, р ¼ 0.0282). Similar tendency to more frequent occurrence of Val allele was found while comparing our research results with similar data in different populations of Mongoloids living around the world.
https://doi.org/10.1016/j.freeradbiomed.2018.10.359
Hepatic epigenomic changes associated with chronic oxidative stress in a mouse model of glutathione deficiency Ying Chen*, Ting Zhai, Xiaoqing Yu, Vasilis Vasilou, Yong Zhu Yale University, USA
Purpose: Oxidative stress has been shown to be intimately involved in the pathogenesis of fatty liver disease (FLD). A major factor contributing to oxidative stress is the depletion of glutathione (GSH). Our previous studies in glutamate cysteine ligase modifier subunit (Gclm)-null mice demonstrate that 85% deficiency in hepatic GSH renders mice protected from fatty liver injuries induced by varieties of hepatic insults, including alcohol exposure. It is well-known that epigenetic mechanisms play active roles in modulating gene expression and disease outcome in FLD. The purpose of the current study is to utilize the Gclm-null mouse model to examine in vivo interplay between chronic oxidative stress and DNA methylation at the epigenome level and whether these epigenetic changes are functionally involved in FLD. Methods: we performed DNA methylation profiling in the liver and whole blood using the Mouse Promoter Methylation Array. Genes with CpG sites that were significantly affected by GSH deficiency were further investigated for network and functional enrichment. Results: Among 22,327 gene promoter regions (from -1300bp to þ500bp of the Transcription Start Sites) that were analyzed, in the liver, only 52 and 6 gene promoters were hypo- and hyper-methylated, respectively, in Gclm-null mice relative to wild-type mice, indicating an overall hypomethylated genome associated with low GSH. Interestingly, the DNA methylation profiles in the liver and blood appeared to be comparable irrespective of the genotype, which leads to the possibility of potential circulating biomarker(s) for hepatic epigenetic fingerprints related to chronic oxidative stress. Ingenuity Pathway Analysis (IPA) revealed that hypo-methylated genes in the KO liver are enriched in canonical pathways of protein phosphorylation, RNA transcription, cytoplasm organization and organismal death. Conclusion: our preliminary data indicate that chronic GSH deficiency induces global DNA hypomethylation. The functional significance of observed epigenomic changes is under investigation.
https://doi.org/10.1016/j.freeradbiomed.2018.10.360
0891-5849/
Contents lists available at ScienceDirect
Free Radical Biology and Medicine journal homepage: www.elsevier.com/locate/freeradbiomed
Genetics/Epigenetics
328 329
Prevalence of mitochondrial superoxide dismutase gene Ala16Val polymorphism among Caucasian and Mongoloid adolescents Tatjana A. Bairova*, Oksana A. Ershova, Marina Darenskaya, Lyubov Kolesnikova Scientific Centre for Family Health and Human Reproduction Problems, Russian Federation, Russian Federation
Background: Mitochondrial superoxide dismutase (SOD2) catalyzes the superoxide dismutation into oxygen and hydrogen peroxide. The activity of SOD2 is determined by the SOD2 gene. The SOD2 gene is located on the chromosome 6q25.3. One of the most studied polymorphisms of this gene is polymorphism Ala16Val, which replaces the amino acid alanine with valine in the 16 position of the amino acid sequence. As a result, the alpha-helix of the SOD2 protein is disrupted. The altered protein has a 3040% activity decrease, increasing the susceptibility of the cell to oxidative stress. The prevalence of Val allele of Ala16Val polymorphism varies in different races: 12.5% in Mongoloids, 46.6% in Caucasians. Methods: We examined 119 adolescents aged 14-17 years: 65 Caucasian teenagers (Russians, average age 15.02 7 0.98 years) and 54 Mongoloid teenagers (Buryats, mean age 15.31 7 0.96 years). Genomic DNA was extracted from whole blood by commercial kits. Ala16Val polymorphism was genotyped using a polymerase chain reaction with electrophoresis detection. Results: In the group of Caucasian adolescents, the frequencies of the genotypes Ala / Ala, Ala / Val and Val / Val are 27.7%; 43.1% and 29.2%. The frequency of Val allele is 50.8%. Among Buryats, the genotypes Ala / Ala, Ala / Val and Val / Val were detected in 7.4%; 53.7% and 38.9%, allele Val in 65.7%. This distribution of genotypes frequencies corresponds to the Hardy-Weinberg Law in both samples. Conclusion: Allele Val of Ala16Val polymorphism of superoxide dismutase 2 gene in the group of Buryat adolescents occurs more often than in the group of Russian adolescents (χ² ¼ 4.82, р ¼ 0.0282). Similar tendency to more frequent occurrence of Val allele was found while comparing our research results with similar data in different populations of Mongoloids living around the world.
https://doi.org/10.1016/j.freeradbiomed.2018.10.359
Hepatic epigenomic changes associated with chronic oxidative stress in a mouse model of glutathione deficiency Ying Chen*, Ting Zhai, Xiaoqing Yu, Vasilis Vasilou, Yong Zhu Yale University, USA
Purpose: Oxidative stress has been shown to be intimately involved in the pathogenesis of fatty liver disease (FLD). A major factor contributing to oxidative stress is the depletion of glutathione (GSH). Our previous studies in glutamate cysteine ligase modifier subunit (Gclm)-null mice demonstrate that 85% deficiency in hepatic GSH renders mice protected from fatty liver injuries induced by varieties of hepatic insults, including alcohol exposure. It is well-known that epigenetic mechanisms play active roles in modulating gene expression and disease outcome in FLD. The purpose of the current study is to utilize the Gclm-null mouse model to examine in vivo interplay between chronic oxidative stress and DNA methylation at the epigenome level and whether these epigenetic changes are functionally involved in FLD. Methods: we performed DNA methylation profiling in the liver and whole blood using the Mouse Promoter Methylation Array. Genes with CpG sites that were significantly affected by GSH deficiency were further investigated for network and functional enrichment. Results: Among 22,327 gene promoter regions (from -1300bp to þ500bp of the Transcription Start Sites) that were analyzed, in the liver, only 52 and 6 gene promoters were hypo- and hyper-methylated, respectively, in Gclm-null mice relative to wild-type mice, indicating an overall hypomethylated genome associated with low GSH. Interestingly, the DNA methylation profiles in the liver and blood appeared to be comparable irrespective of the genotype, which leads to the possibility of potential circulating biomarker(s) for hepatic epigenetic fingerprints related to chronic oxidative stress. Ingenuity Pathway Analysis (IPA) revealed that hypo-methylated genes in the KO liver are enriched in canonical pathways of protein phosphorylation, RNA transcription, cytoplasm organization and organismal death. Conclusion: our preliminary data indicate that chronic GSH deficiency induces global DNA hypomethylation. The functional significance of observed epigenomic changes is under investigation.
https://doi.org/10.1016/j.freeradbiomed.2018.10.360
0891-5849/