Siokas Vasileios, Dardiotis Efthimios, Sokolakis Thomas, Kotoula Maria, Tachmitzi Sophia V, Chatzoulis Dimitrios Z, Almpanidou Pavlina, Stefanidis Ioannis, Hadjigeorgiou Georgios M, Tsironi Evangelia E
a Department of Neurology, Laboratory of Neurogenetics , University of Thessaly, University Hospital of Larissa , Larissa , Greece.
b Department of Ophthalmology, Faculty of Medicine, School of Health Sciences , University of Thessaly , Larissa , Greece.
Curr Eye Res. 2017 Jul;42(7):1048-1053. doi: 10.1080/02713683.2016.1276197. Epub 2017 Feb 28.
There is accumulating evidence for genetic susceptibility to the development of diabetic retinopathy (DR). The role of plasminogen activator inhibitor-1 (PAI-1) in DR risk remains controversial.
The present study was designed to investigate possible influence of PAI-1 gene region polymorphisms on the risk of DR and on the risk of developing DR early vs late in the course of type 2 diabetes mellitus (T2DM).
A total of 138 patients with DR, 107 patients with T2DM without DR, and 315 healthy controls were recruited. To cover the majority of the genetic variability across the extended region of PAI-1 gene, five tag single-nucleotide polymorphisms (SNPs) from the HapMap using a pairwise approach and an r ≥ 0.8 and a minor allele frequency (MAF) of >0.05 were identified. Using logistic regression analyses, tag SNPs and haplotypes were tested for associations with DR risk and risk of DR development early or late in the course of T2DM. The generalized odds ratio (OR) was calculated to estimate the mutational load effect on DR development among all participants. Corrections for multiple comparisons were carried out (p-value < 0.01).
A significant effect of rs2070682 on the risk of early DR onset was found in the codominant model of inheritance [odds ratio, OR (95% confidence interval, CI): 5.04 (1.47-17.28), p = 0.018]. However, this association marginally did not survive multiple testing corrections. No other significant association between PAI-1 tag-SNPs and haplotypes was revealed. Furthermore, no significant mutational load effect of PAI-1 tag SNPs on the risk of DR development in T2DM course was found.
In conclusion, the present study does not provide any strong evidence that PAI-1 gene variants are implicated in the risk of DR or the development of DR during T2DM course.
越来越多的证据表明糖尿病视网膜病变（DR）的发生存在遗传易感性。纤溶酶原激活物抑制剂-1（PAI-1）在DR风险中的作用仍存在争议。
本研究旨在调查PAI-1基因区域多态性对DR风险以及2型糖尿病（T2DM）病程中早期与晚期发生DR风险的可能影响。
共招募了138例DR患者、107例无DR的T2DM患者和315名健康对照。为涵盖PAI-1基因扩展区域的大部分遗传变异性，采用成对方法从HapMap中鉴定了五个标签单核苷酸多态性（SNP），r≥0.8且次要等位基因频率（MAF）>0.05。使用逻辑回归分析，测试标签SNP和单倍型与DR风险以及T2DM病程中早期或晚期发生DR风险的关联。计算广义优势比（OR）以估计所有参与者中突变负荷对DR发生的影响。进行多重比较校正（p值<0.01）。
在共显性遗传模型中发现rs2070682对早期DR发病风险有显著影响[优势比，OR（95%置信区间，CI）：5.04（1.47-17.28），p = 0.018]。然而，这种关联在多重检验校正后勉强未通过。未发现PAI-1标签SNP与单倍型之间的其他显著关联。此外，未发现PAI-1标签SNP对T2DM病程中DR发生风险有显著的突变负荷影响。
总之，本研究没有提供任何有力证据表明PAI-1基因变异与DR风险或T2DM病程中DR的发生有关。
