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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.

Tang, TS; Prior, SL; Li, KW; Ireland, HA; Bain, SC; Hurel, SJ; Cooper, JA; (2012) Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis , 22 (5) 417 - 425. 10.1016/j.numecd.2010.08.001.

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Abstract

Glutathione peroxidase-1 (GPx-1) is an endogenous anti-oxidant enzyme. The T allele of the GPx-1 rs1050450 (C > T) gene variant is associated with reduced enzyme activity. Our aim was to examine the association between this gene variant and peripheral neuropathy in two cross-sectional samples of subjects with diabetes: (i) 773 Caucasian subjects were genotyped from the UCL Diabetes and Cardiovascular disease Study (UDACS) and (ii) 382 Caucasian subjects from the Ealing Diabetes Study (EDS). Peripheral neuropathy status (and oxidised-LDL [Ox-LDL:LDL] and plasma Total Ant-ioxidant Status [TAOS] in UDACS), were analysed in relation to genotype. We observed that: (i) In UDACS, the odds ratio (OR) for peripheral neuropathy in the T allele carriers compared to the CC genotype was 1.61 [1.10-2.28], p = 0.01. This remained significant after adjustment for other risk factors. Ox-LDL:LDL ratio was significantly elevated in T allele carriers (CC vs. CT/TT: 16.3 ± 2.4 v 18.0 ± 2.9 U/mmol LDL, p = 0.02). (ii) In EDS, the OR for peripheral neuropathy in the T allele carriers compared to the CC genotype was 1.95 [1.11-3.42], p = 0.02. This remained significant after adjustment for other risk factors. In conclusion, we observed a significant association between the T allele and peripheral neuropathy and LDL oxidation. This is the first paper to examine the rs1050450 variant in two samples of Caucasian subjects with diabetes. Prospective analysis of the gene variant is required in diabetic and healthy cohorts with measured plasma markers of oxidative stress to investigate the described association further.

Type: Article
Title: Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus.
Location: Netherlands
DOI: 10.1016/j.numecd.2010.08.001
Language: English
Keywords: Aged, Alleles, Antioxidants, Biological Markers, Case-Control Studies, Cross-Sectional Studies, Diabetic Neuropathies, European Continental Ancestry Group, Female, Gene Frequency, Genetic Association Studies, Glutathione Peroxidase, Humans, Lipoproteins, LDL, London, Male, Middle Aged, Oxidative Stress, Polymorphism, Single Nucleotide
UCL classification: UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
URI: http://discovery.ucl.ac.uk/id/eprint/1357201
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