title: Lymphotoxin-alpha C804A polymorphism is a risk factor for stroke. The PROSPER study.
abstract: Inflammation plays a prominent role in the development of atherosclerosis, which is the most important risk factor for vascular events. Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine and is found to be expressed in atherosclerotic lesions. We investigated the association between the C804A polymorphism within the LTA gene and coronary and cerebrovascular events in 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). The primary endpoint was the combined endpoint of death from coronary heart disease, non-fatal myocardial infarction, and clinical stroke. Secondary endpoints were the coronary and cerebrovascular components separately. All associations were assessed with a Cox-proportional hazards model adjusted for sex, age, pravastatin use, and country. Our overall analysis showed a significant association between the C804A polymorphism and the primary endpoint (p = 0.03). After stratification for gender, this association was found only in males. Furthermore, we found that the association between the C804A polymorphism and the primary endpoint was mainly attributable to clinical strokes (p = 0.02). The C804A polymorphism in the LTA gene associates with clinical stroke, especially in men. But further research is warranted to confirm our results.
authors.affiliation: Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands. s.trompet@lumc.nl
authors.forename: S
authors.initials: S
authors.lastname: Trompet
authors.forename: A J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: P
authors.initials: P
authors.lastname: Slagboom
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: G J
authors.initials: GJ
authors.lastname: Blauw
authors.forename: M B
authors.initials: MB
authors.lastname: Murphy
authors.forename: E L E M
authors.initials: EL
authors.lastname: Bollen
authors.forename: B M
authors.initials: BM
authors.lastname: Buckley
authors.forename: I
authors.initials: I
authors.lastname: Ford
authors.forename: A
authors.initials: A
authors.lastname: Gaw
authors.forename: P W
authors.initials: PW
authors.lastname: Macfarlane
authors.forename: C J
authors.initials: CJ
authors.lastname: Packard
authors.forename: D J
authors.initials: DJ
authors.lastname: Stott
authors.forename: R G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003327:Coronary Disease / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D020521:Stroke / Q000235:genetics*
chemical_list: D008233:Lymphotoxin-alpha