title: Human genetic evidence that OX40 is implicated in myocardial infarction.
abstract: We recently showed that genetic variants in OX40L are associated with myocardial infarction (MI) and severity of coronary artery disease in human. A number of studies also suggest a possible role for OX40 (the OX40L receptor) as a factor contributing to atherosclerosis. In the present study, the OX40 gene was screened for variants associated with precocious MI, using individuals with MI before the age of 60 and controls. Despite the fact that the OX40 gene is highly conserved between species and that relatively few common genetic variants were encountered, an association with MI was seen for a polymorphism in intron 5 (rs2298212). In silico investigation suggested that genetic variation (rs2298211), linked to this intronic variant, is possibly affecting spliceosome function. Our results provide evidence that variants in human OX40 might influence susceptibility to MI. The relevance of these findings is supported by the vital functions fulfilled by OX40 in mammals as reflected by the high level of evolutionary conservation.
authors.affiliation: Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden. Massimiliano.Ria@ki.se
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ria
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Susanna
authors.initials: S
authors.lastname: Boquist
authors.forename: Carl-Göran
authors.initials: CG
authors.lastname: Ericsson
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Jacob
authors.initials: J
authors.lastname: Lagercrantz
mesh_terms: D000293:Adolescent; D000328:Adult; D015897:Comorbidity; D004252:DNA Mutational Analysis; D019317:Evidence-Based Medicine; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human