Ethnic Variation in the Mitochondrial Targeting Sequence Polymorphism of MnSOD

Landeghem, G. F. Van; Tabatabaie, Pedram; Kučinskas, Vaidutis; Saha, N.; Beckman, G.

doi:10.1159/000022873

Cited by 48 publications

(19 citation statements)

References 15 publications

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“…A unique Ala-9Val variant has been identified that alters the targeting of the enzyme to the mitochondria [28,29]. Interestingly, population studies have shown that the heterozygote of the SNP to be the most common genotype in all populations surveyed [30]. The effects of the Ala-9Val are not fully understood and therefore it is difficult to hypothesize as to the effects of the variant on the risk of preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

Placental Anti-Oxidant Gene Polymorphisms, Enzyme Activity, and Oxidative Stress in Preeclampsia

et al. 2008

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The etiology and pathophysiology of preeclampsia are not fully understood. However, oxidative stress has been strongly linked to the occurrence of this multi-system disease. This has led to many theories of the pathogenesis of preeclampsia involving placental oxidative stress. In this study, we hypothesized that polymorphisms of anti-oxidant genes in the placental tissue contributed to susceptibility to preeclampsia. Polymorphisms in copper/zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (MnSOD), glutathione-s-transferase M1 (GSTM1), and glutathione-s-transferase T1 (GSTT1) in the umbilical cord tissue were assayed by polymerase chain reaction (PCR) in 23 nulliparous preeclampsia cases and 32 nulliparous normotensive controls. Corresponding enzyme activity levels and an oxidative stress biomarker (8-isoprostane) of the placental tissue were also measured. In addition, maternal plasma 8-isoprostane levels were also determined. Our results showed that no significant differences in polymorphism frequency of the tested genes, enzyme activity levels or 8-isoprostane levels in the placental tissue were detected between the cases and controls. However, maternal plasma 8-isoprostane level was significantly higher in the cases than in the controls (105.8 vs. 27.9 pg/ml, p = 0.03). In conclusion, our study showed that polymorphisms of CuZn-SOD, MnSOD, GSTM1 and GSTT1 in the placental tissue were not associated with preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Placental Anti-Oxidant Gene Polymorphisms, Enzyme Activity, and Oxidative Stress in Preeclampsia

et al. 2008

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“…SOD2 Ala16Val is a dimorphism caused by a C to T transition, which results in Ala to Val substitution at the À9 position of the mature SOD2 isozyme. Previous studies have shown that the Ala allele frequency in Caucasian populations is around 0.5 (0.47-0.56) [14][15][16][17][32][33][34], whereas in African populations it is a little lower (0.36) (data from the international HapMap project), and in Asian populations is the lowest (0.12-0.36) [29,35,36]. Our results for German (0.548), Japanese (0.128) and Xhosa (0.415) populations were in good agreement with these studies.…”

Section: Nucleic Acidsmentioning

confidence: 99%

Multiplex single base extension method for simultaneous genotyping of non‐synonymous SNP in the three human SOD genes

et al. 2008

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The superoxide dismutases (SOD) are a family of enzymes that function as the first line of antioxidant defense against highly reactive superoxide radicals. In SOD genes, a number of SNP have been identified and their associations with various diseases have been reported. In the present study, we applied a multiplex single base extension technique to genotype multiple non-synonymous SNP in the SOD1, SOD2 and SOD3 genes simultaneously, and examined allele distributions in healthy Caucasian (German), Asian (Japanese) and African (Xhosa) populations. Of the ten SNP investigated, two (SOD2 Ala16Val, SOD3 Ala58Thr) were polymorphic in all three ethnic groups and the genotype distributions showed significant inter-group differences. On the other hand, a small number of heterozygotes were observed for three SNP (SOD2 Ser10Ile, SOD3 Ala91Thr, SOD3 Arg231Gly) and no heterogeneity was observed for the remaining five (SOD1 Thr40Ile, SOD1 Asn87Ser, SOD2 Arg156Trp, SOD2 Gly76Arg, SOD2 Glu66Val). Analyses of associations between SOD genotypes and levels of plasma SOD activity demonstrated that SOD2 Ala16Val, a dimorphism leading to substitution in the mitochondrial targeting sequence of SOD2, significantly influences plasma SOD2 activity, and that SOD3 Arg231Gly, leading to substitution in the heparin-binding domain of SOD3, significantly influences plasma total SOD activity.

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“…18 In this latter population, the alanine variant of Mn-SOD has been associated with an increased risk of breast cancer in premenopausal women,19,20 sporadic motor neurone disease,21 diabetic nephropathy,22 and ALD,5 whereas the association with Parkinson's disease, first observed in the Japanese," has not been confirmed in a subsequent study performed in Germany. 23 In contrast to the French study, we found no association between the alanine-Mn-SOD allele and advanced ALD in our cohort of 499 patients.…”

Section: Discussionmentioning

confidence: 95%

Valine-alanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis

Stewart¹,

Leathart

Chen

et al. 2002

Hepatology

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The role of genetic factors in the pathogenesis of alcohol‐induced liver disease (ALD) is receiving increasing attention. Recently, it has been reported that homozygosity for a valine to alanine substitution in the mitochondrial targeting sequence of manganese superoxide dismutase (Mn‐SOD) represents a risk factor for severe ALD. Because this mutation is postulated to modify enzyme transport into mitochondria, we have sought confirmatory evidence of this association in a larger group of patients and investigated whether this polymorphism might influence alcohol‐induced oxidative stress. Genotyping for the valinealanine (Val‐Ala) polymorphism of the Mn‐SOD gene in 281 patients with advanced ALD (cirrhosis/fibrosis) and 218 drinkers without liver disease showed no differences in either the heterozygote (55% vs. 50%) or the homozygote (19% vs. 23%) frequency for the alanine allele. By measuring the titers of circulating antibodies against oxidized cardiolipin (OX‐CL) and malondialdehyde (MDA) or hydroxy‐ethyl radical (HER) adducts as markers of oxidative stress, we found a significant increase in ALD patients compared with healthy controls. However, the carriers of the alanine Mn‐SOD allele had titers of anti‐MDA, anti‐HER, and anti‐OX‐CL IgG comparable with heterozygotes and patients homozygous for the valine allele. Similarly, the frequency of subjects with antibody titers above the 95th percentile of controls was not increased among homozygotes for the alanine Mn‐SOD allele. In conclusion, in our population Val‐Ala polymorphism in Mn‐SOD influences neither susceptibility to alcohol‐induced liver fibrosis nor alcohol‐induced oxidative stress. (HEPATOLOGY2002;36:1355‐1360).

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Ethnic Variation in the Mitochondrial Targeting Sequence Polymorphism of MnSOD

Cited by 48 publications

References 15 publications

Placental Anti-Oxidant Gene Polymorphisms, Enzyme Activity, and Oxidative Stress in Preeclampsia

Placental Anti-Oxidant Gene Polymorphisms, Enzyme Activity, and Oxidative Stress in Preeclampsia

Multiplex single base extension method for simultaneous genotyping of non‐synonymous SNP in the three human SOD genes

Valine-alanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis

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