Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea SA2 8PP, UK.
Nutr Metab Cardiovasc Dis. 2012 May;22(5):417-25. doi: 10.1016/j.numecd.2010.08.001. Epub 2010 Dec 24.
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.
谷胱甘肽过氧化物酶 1（GPx-1）是一种内源性抗氧化酶。GPx-1 rs1050450（C>T）基因变异的 T 等位基因与酶活性降低有关。我们的目的是在两个糖尿病横断面样本中研究该基因变异与周围神经病变之间的关系：（i）773 名白种人受试者来自 UCL 糖尿病和心血管疾病研究（UDACS）并进行了基因分型；（ii）382 名白种人受试者来自伊灵糖尿病研究（EDS）。在 UDACS 中，分析了周围神经病变状态（以及氧化型 LDL [Ox-LDL:LDL] 和血浆总抗氧化状态 [TAOS]）与基因型的关系。我们观察到：（i）在 UDACS 中，与 CC 基因型相比，T 等位基因携带者的周围神经病变的比值比（OR）为 1.61 [1.10-2.28]，p=0.01。在调整其他危险因素后，这仍然具有统计学意义。T 等位基因携带者的 Ox-LDL:LDL 比值显著升高（CC 与 CT/TT：16.3±2.4 与 18.0±2.9 U/mmol LDL，p=0.02）。（ii）在 EDS 中，与 CC 基因型相比，T 等位基因携带者的周围神经病变的 OR 为 1.95 [1.11-3.42]，p=0.02。在调整其他危险因素后，这仍然具有统计学意义。总之，我们观察到 T 等位基因与周围神经病变和 LDL 氧化之间存在显著关联。这是第一篇在两个白种人糖尿病样本中研究 rs1050450 变异的论文。需要对糖尿病和健康队列进行基因变异的前瞻性分析，并测量氧化应激的血浆标志物，以进一步研究描述的关联。
