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Association of genetic polymorphisms of PON1 and CETP with the presence of metabolic syndrome; the effects of genotypes on their serum activity and concentrations


Behdokht Fathi Dizaji
Mahdi Rivandi
Ali Javandoost
Maryam Saberi Karimian
Atena Raei
Amirhossein Sahebkar
Gordon Ferns
Majid Ghayour Mobarhan
Alireza Pasdar

Abstract

Background: The Metabolic syndrome (MetS) is associated with an increased risk of cardiovascular disease and type 2 diabetes. PON1 and CETP genes may be involved in the pathogenesis of lipid metabolism
and thus MetS. Several single nucleotide polymorphisms of genes were demonstrated to affect their function. Curcumin (diferuloylmethane) is a yellow pigment of turmeric that has shown numerous pharmacological
activity against obesity and related conditions through anti-oxidant/anti-inflammatory properties.
Objective: We aimed to assess the association of these polymorphisms with metabolic syndrome and to investigate if these genetic variants were associated with an altered activity of PON1 and the protein levels of CETP at base line and after Curcumin supplementation.
Methods: The genotypes of PON1 and CETP polymorphisms were determined in 81 patients with MetS and 100 healthy individuals using ARMS-PCR and PCR-RFLP techniques.
Results: Individuals with different genotypes of the PON1 rs662, rs854560 and rs705379 polymorphisms did not differ with paraoxonase activity and CETP serum protein concentrations, either at baseline, or after intervention. Individuals with different PON1 rs854560 genotypes differ significantly in serum arylesterase activities (p = .037). There were statistically significant differences in genotype frequencies between cases and controls for CETP rs5882 genotypes (p-value = .034) but not in genotype frequencies and haplotypes for PON1 studied polymorphisms (p-value < .05). The odds ratio for CETP rs5882 was statistically significant using a dominant model. OR (95% CI) = 0.48 (025–0.92), p-value = .029.
Conclusions: There were no associations between the PON1 polymorphisms, or haplotypes with MetS. There was an association between CETPrs5882 and metabolic syndrome. AA genotype of  CETPrs5882 appeared to be protective against MetS in our studied population. There were no association between the PON1 and CETP polymorphisms with PON1enzymatic activities and CETP protein levels at base line and after curcumin supplementation.

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eISSN: 1110-8630