Association between the rs1050450 glutathione peroxidase-1 (C &gt; T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus

Tang, Ting; Prior, Sarah L.; Li, K; Ireland, H; Baín, Steve; Hurel, SJ; Cooper, Jackie A.; Humphries, Steve E.; Stephens, Jeffrey W.

doi:10.1016/j.numecd.2010.08.001

Cited by 44 publications

(33 citation statements)

References 35 publications

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“…This is in line with other reports from Caucasian populations (Tang et al 2012; Kasznicki et al 2016). Such association was reported in the studies from Asia (Hamanishi et al 2004; Tang et al 2008).…”

Section: Discussionsupporting

confidence: 94%

“…The main finding is that the T allele of the Pro198Leu polymorphism might increase risk of DPN. The similar result was obtained by Tang et al (2012). In a study of two independent samples of Caucasian patients with diabetes mellitus, the authors observed a significant association between the T allele of the Pro198Leu polymorphism and peripheral neuropathy.…”

Section: Discussionsupporting

confidence: 91%

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Pro198Leu Polymorphism in the Glutathione Peroxidase 1 Gene Contributes to Diabetic Peripheral Neuropathy in Type 2 Diabetes Patients

et al. 2016

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Glutathione peroxidase 1 (Gpx1) is an endogenous antioxidant enzyme. The T allele of the Pro198Leu polymorphism in the Gpx1 (rs1050450, 198C > T) gene is associated with reduced enzyme activity. The aim of this study was to evaluate the association between Pro198Leu polymorphism and risk of diabetic peripheral neuropathy (DPN). We examined 1244 T2DM patients and 730 healthy controls. In the patient group, 33 % had diabetic peripheral neuropathy. All subjects were genotyped for the Gpx1 Pro198Leu polymorphism by polymerase chain reaction and restriction analysis. A significant increase in the T allele and TT genotype frequencies was observed in DPN patients compared to those without DPN (OR 1.55, 95 % CI 1.30–1.85 and 1.89, 95 % CI 1.30–2.74, respectively). The association remained significant after correction for age, disease duration, HbA1c and BMI. When distribution of T allele was compared between DPN+ and DPN− subgroups and controls, OR was 1.54 for DPN+ and 1.00 for DPN− patients. In conclusion, our findings suggest that Gpx1 Pro198Leu genotypes are significantly associated with the risk of diabetic peripheral neuropathy in patients with T2DM. The study provides new clinically relevant information regarding genetic determinants of susceptibility to diabetic neuropathy.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 91%

Pro198Leu Polymorphism in the Glutathione Peroxidase 1 Gene Contributes to Diabetic Peripheral Neuropathy in Type 2 Diabetes Patients

et al. 2016

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“…A recent meta analysis of 14,372 cancer cases with different tumor types has shown that rs1050450 T allele carries an increased cancer risk [41]. A significant association between this allele and peripheral neuropathy among two independent populations with diabetes has been shown [42]. This allele is also associated with the well-known Kashin Beck disease among the Han Chinese populations [43].…”

Section: Introductionmentioning

confidence: 99%

Understanding Heterogeneity in Supplementation Effects of Selenium in Men: A Study of Stratification Variables and Human Genetics in a Prospective Sample from New Zealand

Ferguson¹,

Karunasinghe²,

Zhu³

et al. 2012

CPPM

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There is marked controversy on the beneficial levels of selenium (Se) to be used as a dietary supplement. The form of supplemented Se and the baseline plasma or serum Se status among supplemented populations are generally considered as crucial factors in this controversy. However, responses to supplemented Se can further vary with other factors, including health status, lifestyle, demographics and genetics. In the present study, the putative supplementation benefits of Se as 200 µg/day selenised yeast for six months were evaluated among a stratified male population from Auckland, New Zealand. Our study considered changes in surrogate biomarkers for cancer including antioxidant selenoenzymes glutathione peroxidase (GPx) and thioredoxin reductase activity (TR) levels, basal and peroxide-induced DNA damage levels. A total of 569 subjects self-reporting a European ancestry signed in for the study and provided answers to a basic demographic, health and lifestyle questionnaire. The effects of Se supplementation on biomarkers showed significant variability based on age, BMI, health status and seleno-genotypes of SELS rs4965373, GPx1 rs1050450, and SEPP1 rs3877899. The data indicate that the benefits of supplementary Se vary significantly across a population, based on demographics, lifestyle, health conditions and seleno-genotypes. As a contrast to "one-size-fits-all" nutritional interventions, these observations collectively inform rational targeting and personalisation of future Se-based dietary supplementation in regards to cancer chemoprevention strategies. This work also represents a way forward in critically understanding Se requirements in populations.

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“…They found that the ACE I/D polymorphism was associated with increased risk of diabetic peripheral neuropathy (p = 0.006) [99]. Tang et al examined the association between the T allele of rs1050450 in glutathione peroxidase-1 (GPx-1) and peripheral neuropathy in two crosssectional samples of subjects with diabetes: 1) 773 Caucasian subjects were genotyped by the University College London Diabetes and Cardiovascular disease Study (UDACS) and 2) 382 Caucasian subjects from the Ealing Diabetes Study (EDS) [100]. The ORs for peripheral neuropathy in T allele carriers compared to the CC genotype were 1.61 (95% CI: 1.10-2.28, p = 0.01) in UDACS and 1.95 (95% CI: 1.11-3.42, p = 0.02) in EDS.…”

Section: Candidate Gene Association Studiesmentioning

confidence: 99%

Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy

Davoudi¹,

Sobrin²

2015

Rev Diabet Stud

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■ AbstractBoth type 1 and type 2 diabetes mellitus can lead to the common microvascular complications of diabetic retinopathy, kidney disease, and neuropathy. Diabetic patients do not universally develop these complications. Long duration of diabetes and poor glycemic control explain a lot of the variability in the development of microvascular complications, but not all. Genetic factors account for some of the remaining variability because of the heritability and familial clustering of these complications. There have been a large number of investigations, including linkage studies, candidate gene studies, and genome-wide association studies, all of which have sought to identify the specific variants that increase susceptibility. For retinopathy, several genomewide association studies have been performed in small or midsize samples, but no reproducible loci across the studies have been identified. For diabetic kidney disease, genomewide association studies in larger samples have been performed, and loci for this complication are beginning to emerge. However, validation of the existing discoveries, and further novel discoveries in larger samples is ongoing. The amount of genetic research into diabetic neuropathy has been very limited, and much is dedicated to the understanding of genetic risk factors only. Collaborations that pool samples and aim to detect phenotype classifications more precisely are promising avenues for a better explanation of the genetics of diabetic microvascular complications.

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Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus

Cited by 44 publications

References 35 publications

Pro198Leu Polymorphism in the Glutathione Peroxidase 1 Gene Contributes to Diabetic Peripheral Neuropathy in Type 2 Diabetes Patients

Pro198Leu Polymorphism in the Glutathione Peroxidase 1 Gene Contributes to Diabetic Peripheral Neuropathy in Type 2 Diabetes Patients

Understanding Heterogeneity in Supplementation Effects of Selenium in Men: A Study of Stratification Variables and Human Genetics in a Prospective Sample from New Zealand

Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy

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