The association of AGER and ALDH2 gene polymorphisms with diabetic retinopathy

To evaluate the possible associations between AGER (rs1051993, rs2070600) and ALDH2 (rs671) gene polymorphisms with nonproliferative (NPDR) and proliferative (PDR) diabetic retinopathy, in a well-defined Greek population.

66 NPDR patients and 57 PDR patients participated in our study, along with 156 age- and gender-matched healthy-control subjects (CL). All the participants underwent a complete ophthalmological examination, while clinical and demographic data were collected. Furthermore, they were genotyped for the studied polymorphisms.

No significant differences were detected among the studied groups regarding the participants' age and gender status. We found that the ALDH2 AA genotype was significantly more frequent in PDR patients than in CL (p = 0.014). Furthermore, between NPDR and PDR groups, the AGER rs1051993 GT and TT genotype frequencies were significantly elevated in PDR patients (p < 0.0001 and 0.04, respectively). Moreover, we demonstrated that the heterozygous GT genotype in DR patients is accompanied by 71.11 times higher risk of developing PDR (OR = 71.11: 95% CI- 4.14-1215.2), while the homozygous TT genotype is associated with 12.71 times elevated risk for PDR development (OR = 12.71: 95% CI- 0.63-254.1).

We documented that the ALDH2 AA and AGER rs1051993 GT and TT genotypes were observed significantly more frequently in PDR Greek diabetic patients. Our findings also support the genetic theory, suggesting that heritability is significantly implicated in the development of DR, providing additional evidence in the understanding of DR pathogenesis.