Genetic variants of tumor necrosis factor superfamily, member 4 (TNFSF4), and risk of incident atherothrombosis and venous thromboembolism.
BACKGROUND
Recent data have implicated tumor necrosis factor (ligand) superfamily, member 4 (TNFSF4) gene variation in myocardial infarction in women; however, no prospective data are available on either incident arterial or venous disorders.


METHODS
We evaluated 2 previously characterized TNFSF4 gene variants (-921C>T and dbSNP rs3850641) with a) incident arterial events using a prospective case-cohort design with 344 incident CVD cases and 2254 control participants, all white, drawn from the Women's Health Study cohort with 10 years of follow-up, and b) venous thromboembolism (VTE) risk using a nested, matched case-control design of 108 white male pairs (drawn from the Physicians' Health Study cohort) and a case-cohort design of white female participants consisting of 125 cases and 2269 controls (drawn from the Women's Health Study cohort), analyzed separately.


RESULTS
Genotype distributions were in Hardy-Weinberg equilibrium. Results from a marker-by-marker regression analysis, adjusting for traditional risk factors, showed a significant association of -921C>T with an increased risk of VTE in women (additive: odds ratio 1.86; 95% CI 1.17-2.92, P = 0.008) in women. Furthermore, using a haplotype-based regression analysis, haplotype C-G was associated with a reduced risk of VTE relative to the referent haplotype, C-A (odds ratio 0.50; 95% CI 0.27-0.92; P = 0.02). In contrast, we found little evidence for an association of the variants/haplotypes with risk of VTE in men or CVD risk in women (as previously reported).


CONCLUSIONS
Our present findings, if corroborated in other prospective investigations, suggest that the TNFSF4 variants tested may be useful indicators for assessing the risk of venous thromboembolism.
Mälarstig
Anders
A
Atherosclerosis Research Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
Eriksson
Per
P
Rose
Lynda
L
Diehl
Kirsti A
KA
Hamsten
Anders
A
Ridker
Paul M
PM
Zee
Robert Y L
RY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000453:epidemiology* / Q000235:genetics; D002545:Brain Ischemia / Q000150:complications; D016022:Case-Control Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D053278:OX40 Ligand / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D013927:Thrombosis / Q000453:epidemiology* / Q000235:genetics; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000235:genetics
D053278:OX40 Ligand; C089251:TNFSF4 protein, human