• HbA1c Modifies Genetic Susceptibility to Severe DR

    By Lynda Seminara
    Selected By: Prem S. Subramanian, MD, PhD

    Journal Highlights

    Investigative Ophthalmology & Visual Science
    2020;61(10):7

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    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.