Association of paraoxonase 1 polymorphism with beta-cell function: a case of molecular heterosis

Paraoxonase 1 (PON1) is an antioxidant enzyme that inhibits the oxidative modification of LDL. Since PON1 has been shown to express in pancreatic islets and oxidative stress plays a role in beta-cell dysfunction, we investigated the impact of the PON1 polymorphisms on beta-cell function. This study included 84 healthy and glucose-tolerant white subjects who underwent an oral glucose tolerance test. Beta-cell function (1stPHS and 2ndPHS) was estimated according to the formulae published by Stumvoll et al. The relationship of the L55M and Q192R polymorphisms to beta-cell function was examined. Allelic frequency in this population was 0.37 for the M allele and 0.30 for the R allele. For the L55M polymorphism, the LM genotype had the lowest 1stPHS (P = 0.009) and 2ndPHS (P = 0.007), indicating molecular heterosis. Multivariate analyses confirmed that the L55M polymorphism was an independent determinant for 1stPHS (P = 0.016) and 2ndPHS (P = 0.009), after adjustment for covariates. For the Q192M polymorphism, no difference was noted in 1stPHS and 2ndPHS. We observed the L55M polymorphism of the PON1 gene as an independent determinant for beta-cell function in glucose-tolerant whites. Our observations suggest that this polymorphism could play a role in beta-cell dysfunction.