Journal Article

Tagging-SNP haplotype analysis of the secretory PLA<sub>2</sub>IIa gene <i>PLA2G2A</i> shows strong association with serum levels of sPLA2IIa: results from the UDACS study

Peter T.E. Wootton, Fotios Drenos, Jackie A. Cooper, Simon R. Thompson, Jeffrey W. Stephens, Eva Hurt-Camejo, Olov Wiklund, Steve E. Humphries and Philippa J. Talmud

in Human Molecular Genetics

Volume 15, issue 2, pages 355-361
Published in print January 2006 | ISSN: 0964-6906
Published online December 2005 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddi453
Tagging-SNP haplotype analysis of the secretory PLA2IIa gene PLA2G2A shows strong association with serum levels of sPLA2IIa: results from the UDACS study

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Recent prospective analysis identified secretory phospholipase A2-IIa (sPLA2IIa) as a coronary artery disease (CAD) risk predictor. This study aimed to examine the relationship between serum levels of sPLA2IIa and variation in the sPLA2IIa gene (PLA2G2A) in a cohort of patients with Type II diabetes (T2D) mellitus. Six tagging single nucleotide polymorphisms (tSNPs) accounting for >92% of the genetic variability in PLA2G2A were identified and distinguished six common haplotypes (frequencies >5%). In the 523 Caucasian T2D patients, levels of sPLA2IIa, independent of CRP, were negatively correlated with total antioxidant status (P=0.003) and high-density lipoprotein cholesterol (P=0.006) in men and correlated with CAD status in women (P=0.002) (Odds ratio of top two tertiles versus bottom=2.50) [95% CI (1.13–5.53) P=0.024]. Overall, tSNP haplotypes showed a highly significant association with sPLA2IIa levels (P<0.0001), explaining 6.3% of the variance. The most common haplotype (frequency 14.2%) was associated with 53% higher sPLA2IIa levels [3.25 ng/ml (±0.14)] compared with the combined other haplotypes [2.13 ng/ml (±0.09), P<0.00001]. Five of the six tSNPs were associated with significant effects on sPLA2IIa levels but the raising haplotype could not be distinguished by a single tSNP and none are likely to be functional. These data confirm the relationship between elevated sPLA2IIa levels and CAD risk reported in both cases: control and prospective analyses. The strong impact of PLA2G2A haplotypic variation on sPLA2IIa levels will help clarify the causality of this association.

Journal Article.  5686 words.  Illustrated.

Subjects: Genetics and Genomics

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