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Updated: Aug 9, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

A novel Val734Ile variant in the ABCC9 gene associated with myocardial infarction

Piercarlo Minoretti1, Colomba Falcone, Alessia Aldeghi

  • 1Department of Cardiology, Alessandro Manzoni Hospital of Lecco, Lecco, Italy.

Clinica Chimica Acta; International Journal of Clinical Chemistry
|March 28, 2006
PubMed

Insights

Genetic variations in the ABCC9 gene are linked to early myocardial infarction (MI). A specific ABCC9 mutation (734Ile allele) significantly increases the risk of MI before age 60.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Genetic Epidemiology

Background:

  • Coronary vasomotor tone alterations are implicated in myocardial infarction (MI).
  • The ATP-binding cassette transporter C9 (ABCC9) gene may regulate coronary artery vasomotility.
  • Investigating genetic variations in ABCC9 for association with early-onset MI is crucial.

Purpose of the Study:

  • To determine if genetic variations in the ABCC9 gene coding sequence are associated with precocious MI (myocardial infarction before age 60).

Main Methods:

  • Screening of the entire ABCC9 coding region using PCR-SSCP analysis in 45 precocious MI patients and 45 matched controls.
  • Analysis of a novel missense mutation (Val734Ile in exon 17) frequency using PCR-RFLPs in a larger Italian cohort (584 MI patients, 873 controls).
  • Multivariate logistic regression analysis adjusting for age, gender, and cardiovascular risk factors.

Main Results:

  • A novel missense mutation, Val734Ile in exon 17 of ABCC9, was identified in one MI patient.
  • Carriers of the rare 734Ile allele showed a 6.40-fold increased risk of MI before age 60 compared to controls (95% CI=1.58-25.90, P=0.009).
  • This association remained significant after adjusting for confounding factors.

Conclusions:

  • The study provides the first evidence linking the newly discovered 734Ile allele in the ABCC9 gene to an increased susceptibility to precocious MI in the studied population.
  • This genetic variant may play a role in the pathogenesis of early-onset myocardial infarction.
  • Further research is warranted to elucidate the functional mechanisms of ABCC9 in coronary artery disease.
Abstract

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