Thrombospondin-2 polymorphism is associated with a reduced risk of premature myocardial infarction.
OBJECTIVE
Recently, polymorphisms in thrombospondin (THBS) genes coding for THBS-1 (N700S), THBS-2 (T>G substitution in 3'-untranslated region), and THBS-4 (A387P) genes were proposed to modulate the risk of premature coronary artery disease (CAD) or myocardial infarction (MI). It was our objective to verify this hypothesis in an independent cohort.


RESULTS
We performed a case-control study among patients (n=503) referred to our institution for symptomatic CAD that occurred before the age of 50 years and a group of age- and sex-matched population-based controls free of CAD (n=1071). The THBS-1 variant allele was not associated with an altered risk of premature CAD or MI. Homozygosity for the THBS-2 variant allele and the THBS-4 variant (387P) allele was significantly associated with a reduced risk of premature MI compared with wild-type individuals (OR=0.44, 0.24 to 0.84 and OR=0.43, 0.22 to 0.85, respectively). The latter observation is in contrast with a previous report, although confidence intervals overlap.


CONCLUSIONS
We conclude that a relationship between the THBS-1 N700S polymorphism and premature CAD is unlikely. For the THBS-4 A387P polymorphism, additional studies are required to elucidate its role in premature CAD. Finally, we conclude that the THBS-2 polymorphism is associated with a reduced risk of premature MI.
Boekholdt
S Matthijs
SM
Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands. s.m.boekholdt@amc.uva.nl
Trip
Mieke D
MD
Peters
Ron J G
RJ
Engelen
Marc
M
Boer
Jolanda M A
JM
Feskens
Edith J M
EJ
Zwinderman
Aeilko H
AH
Kastelein
John J P
JJ
Reitsma
Pieter H
PH
D000328:Adult; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood / Q000235:genetics; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D019699:Thrombospondins / Q000097:blood / Q000235:genetics*; D000099262:Thrombospondin 2
D015815:Cell Adhesion Molecules; D019699:Thrombospondins; D000099262:Thrombospondin 2