Lack of association between endothelin-1 gene variants and myocardial infarction.
OBJECTIVE
Endothelin-1 (ET-1) promotes vasoconstriction and cell proliferation, and has been implicated in hypertension and coronary artery disease. Our aim was to analyse the role of the ET-1 gene (EDN1) in the risk for atherosclerosis/myocardial infarction (MI) in a population with smoking as the prevalent risk factor.


METHODS
The study included 316 patients with early onset MI (<55 years old). All were male with at least one diseased coronary vessel. Denaturing high performance liquid chromatography (DHPLC), single-strand conformation analysis (SSCA), and direct sequencing were used to search for DNA variants in the five EDN1 exons and the promoter region. To determine the association of EDN1 polymorphisms with MI, we genotyped the patients and controls (n=350) and compared the allele and genotype frequencies between groups.


RESULTS
We found six common nucleotide changes: -1394 (T/G) and -974 C/A (promoter), +120 ins/del A (exon 1, 5' UTR), 568 A/G (exon 3, E106E), 844 G/T (exon 5, K198N), and 1617 T/C (exon 5, 3' UTR). No rare EDN1-variants specific to the MIpatients were found. None of the EDN1 polymorphisms were significantly associated with early-onset MI in our population. The two promoter polymorphisms were in linkage disequilibrium with K198N, but no haplotype was associated with MI risk.


CONCLUSIONS
In our population, the EDN1 variation did not contribute to early-onset MI.
Palacín
María
M
Genetica Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
Rodriguez-Pascual
Fernando
F
Reguero
Julián R
JR
Rodríguez
Isabel
I
Avanzas
Pablo
P
Lozano
Iñigo
I
Morís
Cesar
C
Alvarez
Victoria
V
Cannata-Andía
Jorge B
JB
Lamas
Santiago
S
García-Castro
Monica
M
Coto
Eliecer
E
D000328:Adult; D017668:Age of Onset; D000368:Aged; D050197:Atherosclerosis; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D019332:Endothelin-1 / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012907:Smoking
D019332:Endothelin-1