Association of paraoxonase gene polymorphisms with diabetic nephropathy and retinopathy

Emerging reports have revealed a potential association of paraoxonase (PON) gene polymorphisms with diabetic nephropathy (DN) and diabetic retinopathy (DR). However, the identification of susceptible genes and the quantification of associated risks are elusive owing to a lack of reproducibility. Therefore, a meta-analysis was conducted in the present study to improve the understanding of the effect of PON1 and PON2 on DN and DR. A total of 10 articles, involving 2,877 patients and 3,246 controls met the inclusion criteria. Functional variants (n=4) were evaluated, including rs662 (p.Q192R) and rs854560 (p.L55M) in PON1; and rs7493 (p.S311C) and rs12026 (p.A148G) in PON2. Overall, PON1-L55M was found to be significantly associated with DR in all the genetic models: allele [odds ratio (OR)=2.42; 95% confidence interval (CI), 1.91-3.07]; dominant (OR=5.76; 95% CI, 3.14-10.55), homozygote (OR=10.53; 95% CI, 5.59-19.86), heterozygote (OR=3.62; 95% CI, 1.94-6.74), and recessive (OR=3.56; 95% CI, 2.61-4.86), with no evidence of between-study heterogeneity. However, such associations were not detected in DN and the other three polymorphisms did not show any associations with DN or DR. The current meta-analysis highlighted results for the risk of association of PON1-55L with DR. The results also indicated that PON2 gene polymorphisms, as well as PON1-Q192R, may not confer major genetic risk to DN or DR. Additional studies are required to enrich the understanding of PON genes, particularly for its functional role in DR.