Gene-environment interaction between adiponectin gene polymorphisms and environmental factors on the risk of diabetic retinopathy

Abstract

Aims/introduction: To evaluate whether the adiponectin gene is associated with diabetic retinopathy (DR) risk and interaction with environmental factors modifies the DR risk, and to investigate the relationship between serum adiponectin levels and DR.

Materials and methods: Four adiponectin polymorphisms were evaluated in 372 DR cases and 145 controls. Differences in environmental factors between cases and controls were evaluated by unconditional logistic regression analysis. The model-free multifactor dimensionality reduction method and traditional multiple regression models were applied to explore interactions between the polymorphisms and environmental factors.

Results: Using the Bonferroni method, we found no significant associations between four adiponectin polymorphisms and DR susceptibility. Multivariate logistic regression found that physical activity played a protective role in the progress of DR, whereas family history of diabetes (odds ratio 1.75) and insulin therapy (odds ratio 1.78) were associated with an increased risk for DR. The interaction between the C-11377 G (rs266729) polymorphism and insulin therapy might be associated with DR risk. Family history of diabetes combined with insulin therapy also increased the risk of DR. No adiponectin gene polymorphisms influenced the serum adiponectin levels. Serum adiponectin levels did not differ between the DR group and non-DR group.

Conclusions: No significant association was identified between four adiponectin polymorphisms and DR susceptibility after stringent Bonferroni correction. The interaction between C-11377G (rs266729) polymorphism and insulin therapy, as well as the interaction between family history of diabetes and insulin therapy, might be associated with DR susceptibility.

Keywords: Adiponectin; Diabetic retinopathy; Gene–environment interaction.

Figure 1

(a) The identified best model in gene–environment interaction. Distribution of high-risk (dark shading) and low-risk (light shading) combinations associated with diabetic retinopathy (DR) in a gene–environment model. High-risk factors are in the dark gray and low-risk factors are in the light gray. The number of DR patients (left bar in boxes) and control subjects (right bar in boxes) are shown for each square array. A1: insulin therapy, 0 for not taking insulin therapy, 1 for taking insulin therapy; A2: C-11377G (rs266729), 0 for CC genotype, 1 for CG genotype and 2 for GG genotype. (b) The identified best model in environment–environment interaction. High-risk factors are in the dark gray and low-risk factors are in the light gray. The number of DR patients (left bar in boxes) and control subjects (right bar in boxes) are shown for each square array. B1: insulin therapy, 0 for not taking insulin therapy, 1 for taking insulin therapy; B2: family history of diabetes, 0 for not with family history of diabetes, 1 for with family history of diabetes.