A novel Val734Ile variant in the ABCC9 gene associated with myocardial infarction.
BACKGROUND
Alterations in coronary vasomotor tone are deemed to play an important role in myocardial infarction (MI), and the ATP-binding cassette transporter C9-ABCC9-may be involved in the regulation of coronary artery vasomotility. We sought to determine whether genetic variations in the coding sequence of ABCC9 gene could be associated with precocious MI (myocardial infarction before the age of 60 years) in humans.


METHODS
In this study, we screened using PCR-SSCP analysis the entire coding region of the ABCC9 gene in 45 patients with precocious MI and 45 age- and gender-matched controls.


RESULTS
A novel missense mutation, Val734Ile in exon 17, was detected in one MI patient. We therefore analyzed by PCR-RFLPs the frequency of this nonsynonymous change in a large Italian cohort of precocious MI patients (n=584) and healthy comparison subjects (n=873). After allowance for the potential confounding effects of age, gender, and established cardiovascular risk factors, multivariate logistic regression analysis revealed that carriers of the rare 734Ile allele would have a 6.40-fold risk of suffering MI before the age of 60 years as compared to controls (95% CI=1.58-25.90, P=0.009).


CONCLUSIONS
Taken together, our results provide the first important evidence that the newly discovered 734Ile allele in ABCC9 might influence susceptibility to precocious MI in our population.
Department of Cardiology, Alessandro Manzoni Hospital of Lecco, Lecco, Italy.
Piercarlo
P
Minoretti
Colomba
C
Falcone
Alessia
A
Aldeghi
Valentina
V
Olivieri
Francesca
F
Mori
Enzo
E
Emanuele
Margherita
M
Calcagnino
Diego
D
Geroldi
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics*; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000235:genetics*; D011955:Receptors, Drug / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D064233:Sulfonylurea Receptors; D014633:Valine / Q000235:genetics*
C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D007532:Isoleucine; D014633:Valine