P206The interaction of common polymorphisms of the lipoprotein lipase and pon1 genes with cardiovascular risk factors in the phoenix community

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Abstract

Purpose: We investigated gene polymorphisms related to oxidative stress and dyslipidaemia in a sample of subjects with and without metabolic syndrome (MS) from the Phoenix Lifestyle project. Single nucleotide polymorphisms (SNP) in the Human Paraoxonase /PON1 ( Leu55Met and Gln192Arg SNPs) and LPL genes (N291S and S447X SNPs) were studied to investigate the associations of these mutations with cardiovascular risk factors and risk factor clustering in this sample.

Method: There were 1419 subjects from the Phoenix Lifestyle Project cohort who were studied for CV risk factor prevalence and clustering. Anthropometric measurements were performed, with fasting venous blood samples taken from each subject for glucose, lipid and genetic analysis. Genotyping was performed using real-time PCR, allele-specific probes and Melting Curve analysis in a sample of 916 subjects.

Results: The crude prevalence of MS in this sub-cohort, classified according to the IDF criteria was 50%. The LPL and PON 1 genotypes were similarly distributed (p = n/s) in subjects with and without MS. There were no subjects observed with the LPL N291S mutation. There was a significant interaction between the Gln192Arg genotype and elevated triglyceride (> 1.7 mmol/l) levels (p=0.016; OR = 1.356), and in overweight females (BMI>23kg/m2) (p=0.027; OR = 1.911), which was identified in 23% of overweight females.

Discussion: Our study did not support a role for these polymorphisms for predisposition to the MS. Although the S447X, L55M and Q192R polymorphisms are common in this population, only the 192Arg allele, previously associated with reduced protection against lipid peroxidation, predispose to hypertriglyceridaemia in the population, and general obesity in females. Gene polymorphisms related to the MS risk factors may explain a high predisposition to premature atherosclerosis.

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