title: Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus.
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.
authors.affiliation: Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea SA2 8PP, UK.
authors.forename: T S
authors.initials: TS
authors.lastname: Tang
authors.forename: S L
authors.initials: SL
authors.lastname: Prior
authors.forename: K W
authors.initials: KW
authors.lastname: Li
authors.forename: H A
authors.initials: HA
authors.lastname: Ireland
authors.forename: S C
authors.initials: SC
authors.lastname: Bain
authors.forename: S J
authors.initials: SJ
authors.lastname: Hurel
authors.forename: J A
authors.initials: JA
authors.lastname: Cooper
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: J W
authors.initials: JW
authors.lastname: Stephens
mesh_terms: D000368:Aged; D000483:Alleles; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003929:Diabetic Neuropathies / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008131:London; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D044465:White People; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human