The Pro279Leu variant in the transcription factor MEF2A is associated with myocardial infarction.
BACKGROUND
A myocyte enhancer factor 2A (MEF2A) mutation that segregated with coronary artery disease/myocardial infarction (CAD/MI) in a large family has recently been described. Missense mutations in sporadic coronary artery disease patients were also reported. These data suggest that mutations in exons 7 and 11 of MEF2A cause CAD/MI, though the association was refuted by another study.


OBJECTIVE
To analyse the genetic variation of exons 7 and 11 in a large cohort of Spanish CAD/MI patients and controls.


RESULTS
A rare polymorphism, P279L, was detected both in patients and controls. Carriers of the 279Leu allele had a threefold risk of suffering CAD/MI compared with controls (p = 0.009; odds ratio = 3.06 (95% confidence interval, 1.17 to 8.06)). In the controls the allele was found only in those under 50 years of age. Exon 11 showed a high degree of heterogeneity caused by a polyglutamine (CAG)n polymorphism, but no significant differences in genotype or allelic frequencies were found.


CONCLUSIONS
The 279Leu allele appears to be a genetic risk factor for CAD/MI in the population studied. This effect could be the result of a reduced transcriptional activity on MEF2A with 279Leu.
González
P
P
García-Castro
M
M
Reguero
J R
JR
Batalla
A
A
Ordóñez
A G
AG
Palop
R L
RL
Lozano
I
I
Montes
M
M
Alvarez
V
V
Coto
E
E
D000483:Alleles; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007930:Leucine / Q000235:genetics*; D026161:MADS Domain Proteins / Q000235:genetics*; D064326:MEF2 Transcription Factors; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics*; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011392:Proline / Q000235:genetics*
D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D011392:Proline; D007930:Leucine