Paraoxonase gene polymorphisms and haplotype analysis in a stroke population

• Main Authors: Whalley Lawrence (Author), Cheung John (Author), Cumming Alastair (Author), Ross-Adams Helen (Author), Pasdar Alireza (Author), St Clair David (Author), MacLeod Mary-Joan (Author)
• Format: Book
• Published: BMC, 2006-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>Paraoxonase (<it>PON</it>) has anti-atherogenic activity due to its protective function against low density lipoprotein (LDL) oxidation. Alteration of enzyme activity due to polymorphisms in the <it>PON </it>genes may influence the development of atheroma and thus affect stroke risk. Three <it>PON </it>genes (<it>PON1</it>, <it>PON2 </it>and <it>PON3</it>) have been identifiedand mapped to chromosome 7.</p> <p>Methods</p> <p>We looked at the distribution of paraoxonase polymorphisms and haplotype arrangement in 397 Caucasian ischaemic stroke patients and 405 controls. We investigated 6 different common single nucleotide polymorphisms (SNP) in <it>PON </it>genes; two substitutions in <it>PON1 </it>["A/G": Gln (Q)/Arg (R)] at codon 192 and ["T/A": Leu (L)/Met (M)] at codon 55, two in <it>PON2 </it>at codon 311 ["G/A": Cys (C)/Ser (S)] and codon 148 ["C/G": Ala (A)/Gly (G)] and two SNPs, both "A" to "G" substitutions, in <it>PON3 </it>- intronic rs2074353, which we designated <it>PON3</it>-1 and [Ala (A)/Ala (A)] at codon 99, designated as <it>PON3</it>-3. Dynamic Allele Specific Hybridisation (DASH) was used as the genotyping assay. Haplotype analysis was performed using both PHASE and EHPLUS programs.</p> <p>Results</p> <p>Genotype and allele frequencies were similar in cases and controls. Lipid profiles were not influenced by <it>PON </it>genotype. Haplotype frequencies for the six loci (<it>PON2</it>-148, <it>PON2</it>-311, <it>PON3</it>-3, <it>PON3</it>-1, <it>PON1</it>-55 and <it>PON1</it>-192) were estimated. Comparison of the two programs showed a significant difference in haplotype arrangements with EHPLUS (p-value = 0.005) but not with PHASE Ver.2 (p-value = 0.12). The 112211 (1 = frequent allele, 2 = rare allele) haplotype arrangement was commoner in cases than controls (p = 0.015), and the 111121 haplotype was commoner in controls (p = 0.006).</p> <p>Conclusion</p> <p>Our study did not identify a role for individual paraoxonase gene polymorphisms in the pathogenesis of ischaemic stroke. Findings of haplotype differences should be confirmed in large scale studies. The importance of using a well-validated haplotype analysis program is also underlined.</p>

Item Description

10.1186/1471-2350-7-28
1471-2350