Association of paraoxonase 1 polymorphism with β-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 β-cell dysfunction, we investigated the impact of the PON1 polymorphisms on β-cell function. This study included 84 healthy and glucose-tolerant white subjects who underwent an oral glucose tolerance test. β-cell function (1stPHSand 2ndPHS) was estimated according to the formulae published by Stumvoll et al. The relationship of the L55M and Q192R polymorphisms to β-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 1stPHSand 2ndPHS. We observed the L55M polymorphism of the PON1 gene as an independent determinant for β-cell function in glucose-tolerant whites. Our observations suggest that this polymorphism could play a role in β-cell dysfunction. ? 2004 Lippincott Williams and Wilkins, Inc.