title: Mutations in exons 2 and 3 of the FOLR1 gene in demented and non-demented elderly subjects.
abstract: We have previously reported six novel mutations in the 5'-UTR of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations we screened patients, referred for investigation of suspected dementia (DGM subgroup) by SSCP and DNA sequencing from the end of exon 1 to the first bases of intron 3. We found 4 sequence variations, FOLR1 g.1314G>A, g.1816delC, g.1841G>A, and g.1928C>T. Pyrosequencing genotyping assays were developed for all of them, and 389 active seniors (AS subgroup) and the 202 DGM patients were genotyped for these mutations. The frequency q of the mutated allele was, among the AS subjects, 0.068, 0.0026, 0.0026, and 0.024 respectively, and among the DGM subjects, 0.067, 0.0076, 0.0078, and 0.023. The g.1816delC and g.1841G>A mutations thus were more frequent in the DGM than in the AS subgroup, but the difference did not reach statistical significance. The mutated alleles, FOLR1 1816(-) and 1841A, always occurred together in the same subjects, suggestive of a rare double-mutant haplotype. The two common polymorphisms, FOLR1 g. 1314G>A and g.1928C>T seemed not to raise tHcy plasma levels, whereas the double-mutated g.1816(-)-g.1841A haplotype may possibly have a slight tHcy-raising effect. Thus, so far 8 novel rare FOLR1 mutations with a combined prevalence of approximately 1.3% in Whites as well as two common polymorphisms with 5% and 13%, respectively, have been demonstrated. Only a few of the rare mutations may potentially be associated with raised plasma tHcy concentrations. No association with dementia was found.
authors.affiliation: Department of Clinical Chemistry, Orebro University Hospital, Orebro, Sweden.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Böttiger
authors.forename: Nils-Olof
authors.initials: NO
authors.lastname: Hagnelius
authors.forename: Torbjörn K
authors.initials: TK
authors.lastname: Nilsson
mesh_terms: D000368:Aged; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003704:Dementia / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D058975:Folate Receptor 1; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000097:blood; D005820:Genetic Testing; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D006710:Homocysteine; D005492:Folic Acid