Houldsworth Annwyne, Hodgkinson Andrea, Shaw Steve, Millward Ann, Demaine Andy G
Molecular Medicine Research Groups, Peninsula College of Medicine and Dentistry, Plymouth, United Kingdom.
Molecular Medicine Research Groups, Peninsula College of Medicine and Dentistry, Plymouth, United Kingdom.
Gene. 2015 Sep 10;569(1):41-5. doi: 10.1016/j.gene.2015.04.006. Epub 2015 Apr 6.
The effective treatment of diabetes and the prevention of diabetic complications may be improved by a better understanding of the antioxidant function of intracellular defences against oxidative stress. Polymorphisms in antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in diabetes and/or in its complications. SOD-2 was investigated in patients with type 1 diabetes mellitus (T1DM) to ascertain if specific genotypes have any protective influences in the pathogenic mechanisms in diabetes and/or in several different complications, including retinopathy, nephropathy and diabetic controls compared to normal healthy controls.
278 (136M:142F) T1DM patients and 135 (72M:63F) normal, healthy controls were investigated for SOD-2 polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution.
A significant difference in the C-9-T genotype was observed between patients and normal controls but not between diabetic controls and patients with complications. There were significantly more of the diabetic control (DC, n=62) group (11.3%) than the patients with diabetic nephropathy (DN, n=73) (1.4%) with the CC genotype (p=0.03 and χ(2)=4.27, OR=9.16 (1.08<OR<204.03)). Further significance was found between normal healthy controls (11.4%) and patients with nephropathy (1.4%) with the genotype CC (p=0.03, χ(2)=4.68, OR=0.11 (0.00<OR<0.87)). No significant differences were found between these groups for the allelic frequency or between the different complication groups after correction for the number of groups. All groups were in Hardy Weinberg equilibrium.
The SNP in SOD-2 results in a substitution of C to T, which causes an amino acid change from alanine to valine. The variation in the SOD-2 leader signal affects the processing efficiency of the enzyme. A significantly greater proportion of the diabetic control group had the CC genotype suggesting antioxidant protection against diabetic nephropathy. The healthy control group also had a higher incidence of the protective genotype, which may suggest protective influences from the antioxidant gene in the CC form.
通过更好地理解细胞内抗氧化防御对氧化应激的功能，或许可以改善糖尿病的有效治疗以及糖尿病并发症的预防。抗氧化基因的多态性可能决定细胞氧化应激水平，这在糖尿病和/或其并发症中起主要致病作用。对1型糖尿病（T1DM）患者的超氧化物歧化酶2（SOD - 2）进行了研究，以确定特定基因型在糖尿病和/或几种不同并发症（包括视网膜病变、肾病）的致病机制中是否具有任何保护作用，并与正常健康对照以及糖尿病对照进行比较。
对278名（136名男性：142名女性）T1DM患者和135名（72名男性：63名女性）正常健康对照进行研究，检测线粒体靶向序列中具有丙氨酸/缬氨酸（C - 9T）替代的SOD - 2多态性。
患者与正常对照之间在C - 9 - T基因型上存在显著差异，但糖尿病对照与有并发症的患者之间无显著差异。CC基因型的糖尿病对照组（DC，n = 62）比例（11.3%）显著高于糖尿病肾病患者组（DN，n = 73）（1.4%）（p = 0.03，χ² = 4.27，OR = 9.16（1.08 < OR < 204.03））。正常健康对照（11.4%）与肾病患者（1.4%）的CC基因型之间也发现有进一步的显著差异（p = 0.03，χ² = 4.68，OR = 0.11（0.00 < OR < 0.87））。校正组数后，这些组之间的等位基因频率或不同并发症组之间未发现显著差异。所有组均处于哈迪 - 温伯格平衡。
SOD - 2中的单核苷酸多态性导致C替换为T，引起氨基酸从丙氨酸变为缬氨酸。SOD - 2前导信号的变化影响该酶的加工效率。糖尿病对照组中具有CC基因型的比例显著更高，表明对糖尿病肾病具有抗氧化保护作用。健康对照组中保护性基因型的发生率也较高，这可能表明CC形式的抗氧化基因具有保护作用。
