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Tagging SNP haploty...
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
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Wootton, P. T. (author)
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Arora, N. L. (author)
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Drenos, F. (author)
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Thompson, S. R. (author)
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Cooper, J. A. (author)
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Stephens, J. W. (author)
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Hurel, S. J. (author)
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- Hurt-Camejo, Eva, 1956 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Wiklund, Olov, 1943 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
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Humphries, S. E. (author)
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Talmud, P. J. (author)
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: Hum Mol Genet. ; 16:12, s. 1437-44
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https://gup.ub.gu.se...
Abstract
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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 II 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 oxLDL/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, PLA2G5 tSNP 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.
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- By the author/editor
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Wootton, P. T.
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Arora, N. L.
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Drenos, F.
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Thompson, S. R.
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Cooper, J. A.
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Stephens, J. W.
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show more...
-
Hurel, S. J.
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Hurt-Camejo, Eva ...
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Wiklund, Olov, 1 ...
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Humphries, S. E.
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Talmud, P. J.
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show less...
- Articles in the publication
- Hum Mol Genet
- By the university
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University of Gothenburg