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Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets.

Publication ,  Journal Article
Sutton, BS; Crosslin, DR; Shah, SH; Nelson, SC; Bassil, A; Hale, AB; Haynes, C; Goldschmidt-Clermont, PJ; Vance, JM; Seo, D; Kraus, WE ...
Published in: Hum Mol Genet
May 1, 2008

Platelet-activating factor acetylhydrolase (PLA2G7) is a potent pro- and anti-inflammatory molecule that has been implicated in multiple inflammatory disease processes, including cardiovascular disease. The goal of this study was to investigate the genetic effects of PLA2G7 on coronary artery disease (CAD) risk in two large, independent datasets with CAD. Using a haplotype tagging (ht) approach, 19 ht single nucleotide polymorphisms (SNPs) were genotyped in CATHGEN case-control samples (cases = 806 and controls = 267) and in the GENECARD Family Study (n = 1101 families, 2954 individuals). Single SNP analysis using logistic regression revealed nine SNPs with significant association in all CATHGEN subjects (P = 0.0004-0.02). CATHGEN cases were further stratified into subgroups based on age of CAD onset (AOO) and severity of disease; 599 young affecteds (YA, AOO <56) and 207 old affected (OA, AOO >56). Significant genetic effects were observed in both OA and YA (P = 0.0001-0.02). The GENECARD probands demonstrated results similar to those seen in the YA CATHGEN cases (P = 0.002-0.05). Of the 19 SNPs genotyped, 3 SNPs result in nonsynonymous coding changes (I198T, A379V and R92H). Two of the coding SNPs, R92H and A379V, constitute two of the most significantly associated SNPs, even after Bonferroni correction and appear to represent independent associations (r(2) = 0.09). Multiple additional polymorphisms in low linkage disequilibrium with these coding SNPs were also strongly associated. In summary, PLA2G7 represents an important, potentially functional candidate in the pathophysiology of CAD based on replicated associations using two independent datasets and multiple statistical approaches. Further functional studies involving a combination of risk alleles are warranted.

Duke Scholars

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

May 1, 2008

Volume

17

Issue

9

Start / End Page

1318 / 1328

Location

England

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Phospholipases A2
  • North Carolina
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genetics & Heredity
 

Citation

APA
Chicago
ICMJE
MLA
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Sutton, B. S., Crosslin, D. R., Shah, S. H., Nelson, S. C., Bassil, A., Hale, A. B., … Hauser, E. R. (2008). Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets. Hum Mol Genet, 17(9), 1318–1328. https://doi.org/10.1093/hmg/ddn020
Sutton, Beth S., David R. Crosslin, Svati H. Shah, Sarah C. Nelson, Anthony Bassil, A Brent Hale, Carol Haynes, et al. “Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets.Hum Mol Genet 17, no. 9 (May 1, 2008): 1318–28. https://doi.org/10.1093/hmg/ddn020.
Sutton BS, Crosslin DR, Shah SH, Nelson SC, Bassil A, Hale AB, et al. Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets. Hum Mol Genet. 2008 May 1;17(9):1318–28.
Sutton, Beth S., et al. “Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets.Hum Mol Genet, vol. 17, no. 9, May 2008, pp. 1318–28. Pubmed, doi:10.1093/hmg/ddn020.
Sutton BS, Crosslin DR, Shah SH, Nelson SC, Bassil A, Hale AB, Haynes C, Goldschmidt-Clermont PJ, Vance JM, Seo D, Kraus WE, Gregory SG, Hauser ER. Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets. Hum Mol Genet. 2008 May 1;17(9):1318–1328.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

May 1, 2008

Volume

17

Issue

9

Start / End Page

1318 / 1328

Location

England

Related Subject Headings

  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Phospholipases A2
  • North Carolina
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genetics & Heredity