Decreased frequency of the 3′UTR T>G single nucleotide polymorphism of thrombospondin-2 gene in sudden death due to plaque erosion

Abstract 

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≤.0001).

Conclusion

The T>G THBS2 is decreased only in plaque erosion, with no difference in frequency between other coronary disease and controls.

Keywords: Coronary thrombosis, Single nucleotide polymorphism, Thrombospondin