title: CALHM1 P86L polymorphism is associated with late-onset Alzheimer's disease in a recessive model.
abstract: CALHM1 gene coding non-synonymous SNP P86L (rs2986017) was reported to increase the risk of Alzheimer's disease (AD) in a recent study. We have investigated this genetic variant in 2470 individuals from Spain to conduct an independent replication study of the proposed SNP marker. By applying a recessive model, we observed weak evidence of an association between P86L mutation and late-onset AD (LOAD) susceptibility in our case-control study (OR =1.38 C.I. = [1.01-1.89]). Meta-analysis of available studies also supports a recessive model for CALHM1 P86L variant and provides evidence of between study heterogeneity. Importantly, we found that adjusted mean age at AD onset in P86L homozygous LOAD patients was significantly earlier that in the rest of patients (77.01 +/- 6.1 for P86L homozygous carriers versus 79.0 +/- 6.0 for the rest of patients, p=0.002). We concluded that the CALMH1 gene may contribute to AD risk in our study population. The observed genetic model (recessive) and the estimated magnitude of the effect both imply that virtually all studies performed to date were markedly underpowered to detect this effect and underscore the importance of follow up, replication, and meta-analyses of promising genetic signals.
authors.affiliation: Memory Clinic of Fundació ACE, Institut Català de Neurociencies Aplicades, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Boada
authors.forename: Carmen
authors.initials: C
authors.lastname: Antúnez
authors.forename: Jesús
authors.initials: J
authors.lastname: López-Arrieta
authors.forename: José Jorge
authors.initials: JJ
authors.lastname: Galán
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Morón
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández
authors.forename: Juan
authors.initials: J
authors.lastname: Marín
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Lage
authors.forename: Montserrat
authors.initials: M
authors.lastname: Alegret
authors.forename: Jose M
authors.initials: JM
authors.lastname: Carrasco
authors.forename: Concha
authors.initials: C
authors.lastname: Moreno
authors.forename: Luis M
authors.initials: LM
authors.lastname: Real
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Pérez
authors.forename: Lluís
authors.initials: L
authors.lastname: Tárraga
authors.forename: Agustín
authors.initials: A
authors.lastname: Ruiz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011392:Proline / Q000235:genetics*; D013030:Spain
chemical_list: C530077:CALHM1 protein, human; D015220:Calcium Channels; D008562:Membrane Glycoproteins; D011392:Proline; D007930:Leucine