title: Myocyte enhancing factor-2A in Alzheimer's disease: genetic analysis and association with MEF2A-polymorphisms.
abstract: Polymorphisms at different genes have been proposed as determinants of the risk for developing late-onset Alzheimer's disease (LOAD). Among the several candidate genes are those that encode proteins involved in neuronal degeneration/survival. Studies of primary neuronal cultures supported that members of the myocyte enhancing factor-2 (MEF2) family of transcription factors have an anti-apoptotic effect, regulating the expression of proteins involved in neuronal survival and differentiation. We analysed the MEF2A gene in a total of 357 patients (mean age 72 years, range 60-97 years). Among others, a Pro279Leu in exon 8 and a polyglutamine (CAG) repeat polymorphisms in exon 12 were found. These variants were also genotyped in 495 healthy controls (>50 years old), and the frequencies were statistically compared. Eight patients were 279L (six P/L and two L/L), compared to only one control (2% vs. 0.2%; p=0.004, OR=11.32). There was a significantly higher frequency of 279L-carriers among APOE epsilon4+ (7/154=4.5%), compared to epsilon4- (1/203) (p=0.02). In conclusion, our work suggests that the variation at the MEF2A gene could be involved in the risk of developing LOAD. Because MEF2 has been related with neuronal survival, and the 279L allele has been related with a reduction in the transcriptional activation activity of MEF2A, the effect of this allele could be mediated through a down-regulation of antiapoptotic genes.
authors.affiliation: Genética Molecular-Instituto de Estudios Nefrológicos, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Pelayo
authors.initials: P
authors.lastname: González
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Manuel
authors.initials: M
authors.lastname: Menéndez
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Lahoz
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Ana I
authors.initials: AI
authors.lastname: Corao
authors.forename: María T
authors.initials: MT
authors.lastname: Calatayud
authors.forename: Joaquín
authors.initials: J
authors.lastname: Peña
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Castro
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; 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; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D016017:Odds Ratio; D010455:Peptides / Q000235:genetics; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics
chemical_list: D053327:Apolipoprotein E4; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D010455:Peptides; C097188:polyglutamine; D011392:Proline; D007930:Leucine