High blood sugar plays a prominent role in a cascade of damaging molecular and cellular effects, such as oxidative stress, abnormal glycosylation, and inflammation, that may contribute to the development and severity of diabetic retinopathy.
Blood sugar control is known to be an important modifiable risk factor for diabetic retinopathy (DR). However, whether hemoglobin A1c (HbA1c) as an indicator for blood sugar control could modify genetic susceptibility to severe diabetic retinopathy (DR) needs to be investigated. Therefore this study by Kelvin K. K. Ng, Department of Medicine, The University of Hong Kong, Hong Kong, and colleagues aimed to investigate whether HbA1c could modulate the genetic susceptibility to severe diabetic retinopathy (DR) in Chinese patients with type 2 diabetes.
The study included a total of 3,093 Chinese patients with type 2 diabetes -- 1,051 with sight-threatening DR (STDR) and 2,042 without STDR. 69 top-ranked SNPs identified from previous studies were examined for their association with STDR and proliferative DR as a subgroup analysis.
SNPs showing suggestive associations with DR were examined in the stratified analysis by dichotomized HbA1c (<7% vs. ≥7%). Interaction analysis was performed by including an interaction term of SNP × HbA1c in the regression model.
Key findings of the study include:
- Four SNPs showed suggestive associations with STDR.
- In the stratified analysis, patients with adequate glycemic control (HbA1c <7%) had a 42% lower risk of STDR for carrying each additional protective C allele of COL5A1 rs59126004 (P = 1.76 × 10−4)
- rs59126004 demonstrated a significant interaction with dichotomized HbA1c on the risk of STDR (Pinteraction = 1.733 × 10−3).
- In the subgroup analysis for proliferative DR, the protective effect of rs59126004 was even more pronouncedly demonstrated (P = 8.35 × 10−5) and it showed similar interactions with dichotomized HbA1c (Pinteraction = 1.729 × 10−3).
"Our data provided evidence for possible interactions between HbA1c and COL5A1 rs59126004 on the risk of severe diabetic retinopathy (DR). These findings may provide new insight into the pathophysiologic mechanism of DR," concluded the authors.
The study, "Possible Modifying Effect of Hemoglobin A1c on Genetic Susceptibility to Severe Diabetic Retinopathy in Patients With Type 2 Diabetes," is published in the journal Investigative Ophthalmology & Visual Science.
DOI: https://doi.org/10.1167/iovs.61.10.7
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