title: Polymorphism R92Q of the tumour necrosis factor receptor 1 gene is associated with myocardial infarction and carotid intima-media thickness--the ECTIM, AXA, EVA and GENIC Studies.
abstract: The TNFRSF1A gene was screened for polymorphisms in 95 subjects with premature myocardial infarction (MI), who also had one parent who had an MI. A total of 10 polymorphisms were found: three in the promoter region, two in exons and five in introns. All polymorphisms were genotyped in ECTIM, a case-control study of MI (1815 subjects). The nonsynonymous 92Q allele was found in 1.8, 1.0 and 1.7% of controls from Strasbourg, Belfast and Glasgow - respectively; in cases: 4.2, 2.2 and 3.2%. The population-adjusted odds ratio (OR) for MI associated with allele Q carrying was 2.15 (95% CI: 1.09-4.23). To check its possible implication in atherosclerosis, this polymorphism was then genotyped in the AXA Study (ultrasound examinations of carotid and femoral arteries in the context of an employment medical examination, 733 subjects), the EVA Study (ultrasound examinations of carotid arteries in a study of cognitive and vascular ageing, 1092 subjects) and the GENIC Study (on brain infarction (BI), 912 subjects). In the AXA Study, among smokers, carrying the 92Q allele was positively associated with the presence of a carotid plaque (OR 5.07; 95% CI: 1.64-15.63) and with a thickening of the carotid intima-media thickness (IMT) (0.59 (0.11) vs 0.54 (0.11), P=0.045). In the EVA Study, carriers of allele 92Q had an increased mean carotid IMT (0.70 (0.09) vs 0.67 (0.13), P=0.02). No significant association of the 92Q allele was found with BI in the GENIC Study. Overall, these results may suggest that carriers of the 92Q allele may be at increased risk of atherosclerosis.
authors.affiliation: INSERM U525, Epidemiologic and Molecular Genetics of Cardiovascular Diseases, Paris, France.
authors.forename: Odette
authors.initials: O
authors.lastname: Poirier
authors.forename: Viviane
authors.initials: V
authors.lastname: Nicaud
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gariépy
authors.forename: Dominique
authors.initials: D
authors.lastname: Courbon
authors.forename: Alexis
authors.initials: A
authors.lastname: Elbaz
authors.forename: Caroline
authors.initials: C
authors.lastname: Morrison
authors.forename: Franck
authors.initials: F
authors.lastname: Kee
authors.forename: Alun
authors.initials: A
authors.lastname: Evans
authors.forename: Dominique
authors.initials: D
authors.lastname: Arveiler
authors.forename: Pierre
authors.initials: P
authors.lastname: Ducimetière
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
authors.forename: François
authors.initials: F
authors.lastname: Cambien
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D001120:Arginine / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D020520:Brain Infarction / Q000235:genetics / Q000473:pathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D003430:Cross-Sectional Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology*; D014463:Ultrasonography
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D005973:Glutamine; D001120:Arginine