Wootton, PTE; Arora, NL; Drenos, F; Thompson, SR; Cooper, JA; Stephens, JW; ... Talmud, PJ; + view all Wootton, PTE; Arora, NL; Drenos, F; Thompson, SR; Cooper, JA; Stephens, JW; Hurel, SJ; Hurt-Camejo, E; Wiklund, O; Humphries, SE; Talmud, PJ; - view fewer (2007) Tagging SNP haplotype analysis of the secretory PLA2-V gene, PLA2G5, shows strong association with LDL and oxLDL levels, suggesting functional distinction from sPLA2-IIA: results from the UDACS study. HUM MOL GENET , 16 (12) 1437 - 1444. 10.1093/hmg/ddm094.
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Animal and human studies suggest that both secretory PLA2 (sPLA2)-V and sPLA2-IIA (encoded, respectively, by the neighbouring PLA2G5 and PLA2G2A genes) contribute to atherogenesis. Elevated plasma sPLA2-IIA predicts coronary heart disease (CHD) risk, but no mass assay for sPLA2-V is available. We previously reported that tagging single nucleotide polymorphism (tSNP) haplotypes of PLA2G2A are strongly associated with sPLA2-IIA mass, but not lipid levels. Here, we use tSNPs of the sPLA2-V gene to investigate the association of PLA2G5 with CHD risk markers. Seven PLA2G5 tSNPs genotypes, explaining > 92% of the locus genetic variability, were determined in 519 patients with Type 11 diabetes (in whom PLA2G2A tSNP data was available), and defined seven common haplotypes (frequencies > 5%). PLA2G5 and PLA2G2A tSNPs showed linkage disequilibrium (LD). Compared to the common PLA2G5 haplotype, H1 (frequency 34.9%), haplotypes H2-7 were associated with overall higher plasma LDL (P < 0.00004) and total cholesterol (P < 0.00003) levels yet lower oxLD/LDL (P = 0.006) and sPLA2-IIA mass (P = 0.04), probably reflecting LD with PLA2G2A. Intronic tSNP (rs11573248), unlikely itself to be functional, distinguished H1 from LDL-raising haplotypes and may mark a functional site. In conclusion, PLA2G5tSNP haplotypes demonstrate an association with total and LDL cholesterol and oxLDL/LDL, not seen with PLA2G2A, thus confirming distinct functional roles for these two sPLA2s.
|Title:||Tagging SNP haplotype analysis of the secretory PLA2-V gene, PLA2G5, shows strong association with LDL and oxLDL levels, suggesting functional distinction from sPLA2-IIA: results from the UDACS study|
|Keywords:||LOW-DENSITY LIPOPROTEINS, CORONARY-ARTERY-DISEASE, II PHOSPHOLIPASE A(2), GROUP-V, MYOCARDIAL-INFARCTION, INCREASED AFFINITY, PLASMA-LEVELS, SERUM-LEVELS, HEALTHY-MEN, ATHEROSCLEROSIS|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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