HbA1c Modifies Genetic Susceptibility to Severe DR
Investigative Ophthalmology & Visual Science
Studies of the effect of glycemic control on genetic susceptibility to severe diabetic retinopathy (DR) in type 2 diabetes are limited. Ng et al. expanded on a previous case-control study and found a possible link between the single-nucleotide polymorphism (SNP) COL5A1 rs59126004 and the risk of severe DR, as well as data suggesting that hemoglobin A1c (HbA1c) can modify this genetic susceptibility.
For this study, the researchers evaluated 3,093 Southern Chinese patients with type 2 diabetes. Of these, 2,042 served as controls, and 1,051 had sight-threatening DR. A subset of those with DR (n = 409) had proliferative DR (PDR). Sixty-nine SNPs from previous genome-wide association studies were investigated for a potential relationship with severe DR (subgroup analysis). SNPs that showed possible associations were examined by HbA1c value (<7% vs. ≥7%; stratified analysis) and in a multiple logistic regression model (interaction analysis).
Results showed that patients with sight-threatening DR had longer duration of diabetes, higher HbA1c levels, and greater likelihood of hypertension. After adjustment for traditional risk factors, four SNPs were nominally linked to sight-threatening DR. In the stratified analysis, HbA1c <7% was associated with a 42% lower risk of sight-threatening disease per additional protective C allele of COL5A1 rs59126004 (p = 1.76 × 10-4; odds ratio [OR], 0.58). This effect was not observed with HbA1c ≥7%. In the subgroup analysis for PDR, COL5A1 rs59126004 produced an even stronger protective effect: 63% lower risk of sight-threatening DR per additional C allele (p = 8.35 × 10-5; OR, 0.37). In the gene-environment interaction analysis, COL5A1 rs59126004 showed significant interactions with dichotomized HbA1c on both sight-threatening disease and PDR risk. No other SNP showed significance in the interaction analysis.
Although COL5A1 rs59126004 had a favorable modifying effect on sight-threatening DR and PDR in this study, the authors cautioned that their results are based on a one-time HbA1c measurement rather than a patient’s mean HbA1c throughout the course of diabetes.
Nonetheless, this study adds evidence to support the effect of tight glycemic control in DR prevention.
The original article can be found here.