Paraoxonase 1 (PON1) gene polymorphism and haplotype analysis in type 2 diabetes mellitus: a case–control study in the south Iranian population

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Paraoxonase-1 (PON1) is involved in prevention of lipid peroxidation and has been associated with diseases characterized by high oxidative stress, such as cardiovascular disease and diabetes. It has been studied as a potential candidate gene for diabetes risk, but direct evidence from genetic association studies remains inconclusive. We performed an analysis in order to investigate the association between three PON1 polymorphisms (Q192R, L55M, and −108C>T) with type 2 diabetes mellitus (T2DM) in south Iranian population. A total of 340 individuals (171 documented T2DM patients and 169 healthy controls) were examined in this study. After DNA isolation and PCR-RFLP, the products were analyzed for L55M and Q192R polymorphisms in coding region and for −108C>T in promotor sequence of PON1. Statistical analysis showed that all genotypes of Q192R and −108C>T polymorphisms were not associated with diabetes (P > 0.05). However, in PON1 55 gene polymorphism, the allelic frequency of methionine (M) was significantly higher in T2DM patients compared to controls (37 vs. 28%, P < 0.05). In addition, a strong association was found between the LM+MM group and diabetes (P = 0.006). The results of the haplotype analysis for the combinations of the three polymorphisms in patients were shown that the haplotype L-T-R frequency was significantly lower in patients as compared to the controls with odds ratio of 0.28 (OR = 0.28, 95% CI 0.13–0.60, P = 0.0004). The most frequent haplotype in two patient and control groups was L-C-Q (31 and 30.2%, respectively). Met allele of PON1 55 gene polymorphism is an independent risk factor for T2DM and the L-T-R may represent as a protective haplotype in south Iranian population. Our results showed that the frequencies of polymorphisms of PON1 in the south Iranian population differ to some of those observed in other ethnic groups and provide useful data for epidemiological studies.