Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration

PURPOSE: Paraoxonase (E.C.3.1.1.2) is a polymorphic protein shown to prevent low-density lipoprotein oxidation. Our purpose is to evaluate the hypothesis that paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level play a role in the occurrence of exudative age,related macular degeneration. METHODS: We analyzed paraoxonase genotypes (A/B, Gln-Arg192 and L/M, Leu-Met54) and plasma oxidized low-density lipoprotein levels in 72 unrelated Japanese patients with exudative age,related macular degeneration and compared the results with those of 140 age,matched and sex,matched control subjects. RESULTS: The distribution of paraoxonase 192 and paraoxonase 54 polymorphisms was significantly differs ent between the patients with age-related macular degeneration and control subjects (chi-square = 6.226, P = .0445, and chi-square = 6.863, P = .0323, respectively). The high frequency of the BB genotype at position 192 was observed in the exudative age related macular degeneration group compared with control subjects (52.8% vs 35.0%, respectively; P = .0127). The high frequency of the LL genotype at position 54 was observed in the patients more than the controls (91.7% vs 77.1%, respectively; P = .0090). The mean (+/- SE) oxidized low density lipoprotein levels in the patients was significantly higher than in the controls (19.1 +/- 1.0 vs 16.2 +/- 0.6 U/ml, P < .01). 0 CONCLUSION: These results indicate that the paraoxonase gene polymorphisms may represent a possible genetic risk factor for age-related macular degeneration and that increased plasma oxidized low-density lipoprotein may be involved in the pathogenesis of age-related macular degeneration. (C) 2001 by Elsevier Science Inc. All rights reserved.