Decreased frequency of the 3'UTR T>G single nucleotide polymorphism of thrombospondin-2 gene in sudden death due to plaque erosion.
OBJECTIVE
Clinical studies have suggested a potentially "protective" variant of the thrombospondin gene 2 (THBS2, MIM*188061). Autopsy studies investigating the frequency of THBS2 polymorphisms in different coronary substrates have not been done.


METHODS
We evaluated the frequency of the T>G THBS2 (SNP ID G5755e5) polymorphism in 439 cases of sudden unexpected death, including acute thrombosis occurring on plaque erosion (n=60), acute thrombosis occurring on plaque rupture (n=54), severe coronary artery disease without acute thrombus (n=76), and 249 sudden unexpected deaths without significant coronary disease. Allele types were determined by polymerase chain reaction of DNA extracted from autopsy frozen tissues.


RESULTS
In controls, there were 60.2% wild-type, 35.3 % TG, and 4.4% GG phenotypes. The frequency of G allele carriers (TG or GG) was 23.3% in erosions vs. 39.8% in controls (P=.02). There was no difference in controls vs. plaque ruptures (40.7%) or severe CAD without thrombus (38.2%). By multivariate analysis, lack of G allele (wild-type TT genotype) was associated with plaque erosion [odds ratio (OR) 2.2, P=.02], independent of age, gender, and cigarette smoking. When combined with a history of cigarette smoking, the association between TT genotype and plaque erosion was greater (OR 3.5, P < or = .0001).


CONCLUSIONS
The T>G THBS2 is decreased only in plaque erosion, with no difference in frequency between other coronary disease and controls.
Burke
Allen
A
Department of Pathology, University of Maryland Medical Systems, Baltimore, MD 21201, USA. allen.burke@gmail.com
Creighton
Wendy
W
Tavora
Fabio
F
Li
Ling
L
Fowler
David
D
D000328:Adult; D016893:Carotid Stenosis / Q000235:genetics* / Q000473:pathology; D003328:Coronary Thrombosis / Q000235:genetics / Q000473:pathology; D016757:Death, Sudden, Cardiac / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics*; D000099262:Thrombospondin 2
D019699:Thrombospondins; D000099262:Thrombospondin 2