Association of candidate gene polymorphisms with diabetic retinopathy in Chinese patients with type 2 diabetes

Int J Ophthalmol. 2020 Feb 18;13(2):301-308. doi: 10.18240/ijo.2020.02.15. eCollection 2020.


Aim: To investigate the association between a set of six candidate genes and the risk of diabetic retinopathy (DR) in an urban community cohort of Chinese patients with type 2 diabetes mellitus (T2DM).

Methods: A population-based cross-sectional study. The diabetic subjects were recruited from an urban community in Beijing and categorized into groups of proliferative diabetic retinopathy (PDR), non-proliferative diabetic retinopathy (NPDR), or diabetic without any retinopathy (DWR) based on the fundus photography and duration of diabetes. Six candidate genes, including advanced glycation end product specific receptor (AGER), aldose reductase (AKR1B1), inducible nitric oxide synthase (iNOS), pigment epithelium derived factor (PEDF), tumor necrosis factor-alpha (TNF-α), and paraoxonase 1 (PON1), were chosen based on Meta-analysis of genetic association studies for DR and biochemical pathways implicated in DR progression. The allele and genotype distribution of 21 functional single-nucleotide polymorphisms (SNPs) in those 6 candidate genes were investigated using MassARRAY genotyping system.

Results: Among 1461 diabetic patients recruited from community, 569 were selected in following genotyping analysis, including 97 patients with PDR, 217 with NPDR, and 255 with DWR. For the promoter variant rs1051993 in AGER gene, the distribution of allele and genotype in PDR group differed from that in DWR group (allele: P=0.011; genotype: P=0.01). Compared with DWR, patients with PDR had lower frequencies of heterozygous genotype GT (9.8% for DWR, 1% for PDR, OR: 0.10, 95%CI: 0.01-0.72) and minor allele T (4.9% for DWR, 0.5% for PDR, OR: 0.10, 95%CI: 0.01-0.75). In multivariate model, the distribution of genotype for rs1051993 in PDR group was significantly different from that in DWR group (GT vs GG: OR: 0.07, 95%CI: 0.01-0.61, P<0.001). No association with DR was observed in other genotyped SNPs.

Conclusion: The data suggest a significant association of the promoter variant rs1051993 in AGER gene with PDR in Chinese cohort with T2DM.

Keywords: AGER; AKR1B1; PEDF; PON1; TNF-α; diabetic retinopathy; iNOS; polymorphisms.