Mutations in exons 2 and 3 of the FOLR1 gene in demented and non-demented elderly subjects

• Published in: International journal of molecular medicine Vol. 20; no. 5; pp. 653 - 662
• Main Authors: Böttiger, Anna, Hagnelius, Nils-Olof, Nilsson, Torbjörn
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.11.2007
• Subjects: Aged; Base Sequence; Carrier Proteins - genetics; Dementia - genetics; Dermatologi och venerologi, klinisk genetik, invärtesmedicin; Dermatology and venerology,clinical genetics, internal medicine; DNA Mutational Analysis; Exons - genetics; Female; Folate Receptor 1; Folate Receptors, GPI-Anchored; Folic Acid - blood; Genetic Testing; Geriatrics and medical gerontology; Geriatrik och medicinsk gerontologi; Homocysteine - blood; Humans; Internal medicine; Invärtesmedicin; Male; MEDICIN; MEDICINE; Molecular Sequence Data; Mutation - genetics; Polymorphism, Single Nucleotide - genetics; Receptors, Cell Surface - genetics
• ISSN: 1107-3756; 1791-244X; 1791-244X
• DOI: 10.3892/ijmm.20.5.653

We have previously reported six novel mutations in the 5'-UTR of the gene for folate receptor-α (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 ≈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.