title: Polymorphisms in the paraoxonase and endothelial nitric oxide synthase genes and the risk of early-onset myocardial infarction.
abstract: In young patients, the accumulative burden of traditional cardiovascular risk factors may not be as significant as in an older population. Genetic risk factors were suggested to have a role in the early development of myocardial infarction (MI). However, data about the association between polymorphisms in heart disease-related genes and the early onset of a first MI are limited. In the present study, age at onset of a first MI was related to individual single-nucleotide polymorphisms in each of 18 prespecified candidate genes in a cohort of 814 patients enrolled in the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) Study. Multivariate regression analysis showed in patients who had the high-risk genotypes of paraoxonase 1 (PON1) Q192R and endothelial nitric oxide synthase (eNOS) E298D that ages at onset of a first MI were 1.8 (p = 0.02) and 3.5 years (p = 0.02) earlier than in noncarriers of the genotypes, respectively. Consistently, high-risk genotypes of the PON1 Q192R and eNOS E298D polymorphisms were significantly associated with onset of a first MI at age <50 years (adjusted odds ratio 1.70, p = 0.005, adjusted odds ratio 2.15, p = 0.01, respectively). In conclusion, our findings suggest that high-risk genotypes of the PON1 Q192R and eNOS E298D polymorphisms are independently associated with a significantly earlier occurrence of coronary events.
authors: Cardiology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors: Brian
authors: B
authors: Morray
authors: Ilan
authors: I
authors: Goldenberg
authors: Arthur J
authors: AJ
authors: Moss
authors: Wojciech
authors: W
authors: Zareba
authors: Daniel
authors: D
authors: Ryan
authors: Scott
authors: S
authors: McNitt
authors: Shirley W
authors: SW
authors: Eberly
authors: Galina
authors: G
authors: Glazko
authors: Jehu
authors: J
authors: Mathew
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001224:Aspartic Acid; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D018698:Glutamic Acid; D005973:Glutamine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human