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Tagging-SNP haploty...
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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Wootton, P. T. (author)
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Drenos, F. (author)
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Cooper, J. A. (author)
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Thompson, S. R. (author)
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Stephens, J. W. (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,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Humphries, S. E. (author)
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Talmud, P. J. (author)
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(creator_code:org_t)
- 2006
- 2006
- English.
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In: Hum Mol Genet. ; 15:2, s. 355-61
- Related links:
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https://gup.ub.gu.se...
Abstract
Subject headings
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- Recent prospective analysis identified secretory phospholipase A(2)-IIa (sPLA(2)IIa) as a coronary artery disease (CAD) risk predictor. This study aimed to examine the relationship between serum levels of sPLA(2)IIa and variation in the sPLA(2)IIa 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 sPLA(2)IIa, 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 sPLA(2)IIa levels (P < 0.0001), explaining 6.3% of the variance. The most common haplotype (frequency 14.2%) was associated with 53% higher sPLA(2)IIa 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 sPLA(2)IIa 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 sPLA(2)IIa levels and CAD risk reported in both cases: control and prospective analyses. The strong impact of PLA2G2A haplotypic variation on sPLA(2)IIa levels will help clarify the causality of this association.
Keyword
- Aged
- Cholesterol
- HDL/blood
- Cohort Studies
- Coronary Arteriosclerosis/blood/*etiology
- Diabetes Mellitus
- Type 2/*complications/*enzymology
- European Continental Ancestry Group/genetics
- Female
- Gene Components
- Genotype
- Haplotypes/genetics
- Humans
- Linkage Disequilibrium
- London
- Male
- Middle Aged
- Phospholipases A/*blood/genetics
- Polymorphism
- Single Nucleotide/*genetics
- Risk Factors
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Wootton, P. T.
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Drenos, F.
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Cooper, J. A.
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Thompson, S. R.
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Stephens, J. W.
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Hurt-Camejo, Eva ...
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show more...
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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