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02 December 2003

Missense mutation of exon 3 in the type A human natriuretic peptide receptor gene is associated with myocardial infarction

Tomohiro Nakayama, Masayoshi Soma, Satoshi Saito, Junko Honye, Mikano Sato, Noriko Aoi, Kotoko Kosuge, Akira Haketa, Katsuo Kanmatsuse, Shinichiro Kokubun

Med Sci Monit 2003; 9(12): CR505-510 :: ID: 13422

Abstract

Background:Myocardial infarction (MI) is a complex multifactorial and polygenic disorder that is thought to result from interaction between genetic make-up and various environmental factors. We previously identified a missense mutation, methionine (ATG) to isoleucine (ATC) at nucleotide 1023 (M341I), in exon 3 of the human natriuretic peptide receptor A type (hNPRA) gene. This mutation is associated with increased risk for essential hypertension (EH). The purpose of this study was to investigate association between MI and the M341I mutation in the hNPRA gene.Material/Methods:The study population included 305 healthy control subjects and 230 patients with MI, all of whom were below the age of 70 years. To assess the identified mutation in the target exon using Taq I restriction fragment length polymorphism (RFLP), specific primers were utilized. Based on the results of the PCR-RFLP, we developed a convenient and automatic method for genotyping by allelic discrimination using TaqMan™ PCR chemistry.Results:Multiple logistic linear regression analysis showed significant difference in genotype distribution between the control and MI groups. Overall distribution of alleles also differed significantly between the MI and control groups (p=0.028). The C allele was found more frequently in the MI group than in the control group.Conclusions:We conclude that the M341I missense mutation is associated with risk for MI and may be a genetic marker of MI in Japanese people.

Keywords: Alleles, Base Sequence, Case-Control Studies, DNA Primers - genetics, Exons, Gene Frequency, Genetic Markers, Guanylate Cyclase - genetics, Japan, Mutation, Missense, Myocardial Infarction - genetics, Polymorphism, Restriction Fragment Length, Receptors, Atrial Natriuretic Factor - genetics, Risk Factors

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750