Q192R polymorphism of the paraoxonase-1 gene as a risk factor for obesity in Portuguese women

Abstract

Introduction: Obesity became a major public health problem as a result of its increasing prevalence worldwide. Paraoxonase-1 (PON1) is an esterase able to protect membranes and lipoproteins from oxidative modifications. At the PON1 gene, several polymorphisms in the promoter and coding regions have been identified. The aims of this study were i) to assess PON1 L55M and Q192R polymorphisms as a risk factor for obesity in women; ii) to compare PON1 activity according to the expression of each allele in L55M and Q192R polymorphisms; iii) to compare PON1 activity between obese and normal-weight women. Materials and methods: We studied 75 healthy (35.9G8.2 years) and 81 obese women (34.3G8.2 years). Inclusion criteria for obese subjects were body mass index R30 kg/m 2 and absence of inflammatory/neoplasic conditions or kidney/hepatic dysfunction. The two PON1 polymorphisms were assessed by real-time PCR with TaqMan probes. PON1 enzymatic activity was assessed by spectrophotometric methods, using paraoxon as a substrate. Results: No significant differences were found for PON1 activity between normal and obese women. Nevertheless, PON1 activity was greater (P!0.01) for the RR genotype (in Q192R polymorphism) and for the LL genotype (in L55M polymorphism). The frequency of allele R of Q192R polymorphism was significantly higher in obese women (P!0.05) and was associated with an increased risk of obesity (odds ratioZ2.0 -95% confidence interval (1.04; 3.87)). Conclusion: L55M and Q192R polymorphisms influence PON1 activity. The allele R of the Q192R polymorphism is associated with an increased risk for development of obesity among Portuguese Caucasian premenopausal women.

Significant interethnic differencies in functional variants of PON1 and P2RY12 genes in Roma and Hungarian population samples

“…Finnish [15], British [16] and German [17] studies showed also similarity. Our data of Hungarian population is nearly the same as Portuguese [18], Turkish [19] and Irish [20] populations. There is a large contrast between European and Asian data.…”

Distribution of Paraoxonase 1 polymorphisms and activities in obese patients

“…Recent studies indicate that HDL-associated PON1 may be involved in the pathogenesis of metabolic syndrome and obesity by demonstrating low A-ase, P-ase (6) and L-ase (18) activities and by presenting some associations with less active PON1 gene variants in obese individuals (5,6).…”

“…HDLassociated PON1 hydrolyzes paraoxon, organophosphorus compounds, unsaturated aliphatic esters and aromatic carboxylic esters (2,5). PON1 enzymatic activity is characterized by large interindividual variation and its low values predict a high risk of developing diseases involving oxidative damage and lipid peroxidation (5).…”

“…Various studies have reported significant correlations between obesity and PON1 gene variants (5,6). Controversial results have been obtained when assessing the correlation between obesity and enzymatic activity: some report lower levels of PON1 in obese individuals than in healthy subjects (6).…”

Genotype and phenotype frequencies of paraoxonase 1 in fertile and infertile men

“…Studies have shown that the 192R isoform has higher lactonase activity and higher binding affinity to HDL and hydrolyzes paraoxon faster compared to the 192Q isoform, whereas the 192Q isoform exhibits lower stability and hydrolyzes diazoxon faster [Bhattacharyya et al 2008;Gaidukov et al 2006;Gupta et al 2011;Veiga et al 2011]. In comparison, the 192Q isoform of PON1 is more efficient in reducing total lipidperoxide content and therefore shows higher antioxidant effects [Mackness et al 1998b].…”