Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/44697
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dc.contributor.authorNilsson, Torbjörn K.
dc.contributor.authorLaanpere, Margit
dc.contributor.authorAltmäe, Signe
dc.contributor.authorSerra-Majem, Lluís
dc.contributor.authorSalumets, Andres
dc.date.accessioned2018-11-22T01:45:52Z-
dc.date.available2018-11-22T01:45:52Z-
dc.date.issued2012
dc.identifier.issn0301-4851
dc.identifier.urihttp://hdl.handle.net/10553/44697-
dc.description.abstractFolate is crucial for various cellular functions. Several transport mechanisms allow folate to enter the intracellular compartment with folate receptor-alpha being the major high-affinity receptor. Rare genetic variations in exons of the FR-alpha gene, FOLR1, were recently shown to cause severe folate deficiency accompanied by neurological and other disturbances. So far, similar effects by genetic variation in noncoding parts of the FOLR1 gene have not been identified. The aim of our study was to determine biochemically the haplotype structure of two linked polymorphisms in the FOLR1 gene, 1816delC and 1841G > A, the prevalences of the mutated alleles across Eurasia, and their possible effects on physiological folate levels in vivo. For this purpose we employed allele-specific PCR and Pyrosequencing technology and performed genotyping in 738 subjects from Spain, 387 from Sweden, 952 from Estonia, and 47 from Korea. We demonstrate the presence of an ancient double-mutated haplotype 1816delC-1841A in the FOLR1 gene, with the prevalence of the mutated allele being highest among Koreans (q = 0.074), lower in Estonians (q = 0.017), Spaniards (q = 0.0061), and the lowest among Swedes (q = 0.0026). Erythrocyte folate levels were studied in the Spanish population sample, where subjects carrying the double-mutated FOLR1 haplotype had significantly reduced levels by 27% (P = 0.039), adjusted for serum vitamin B-12 levels and MTHFR 677C > T genotype, while the mean serum folate levels were only 20% lower among the carriers (P = 0.11). Plasma homocysteine and cobalamin levels did not differ. Thus, we have demonstrated by molecular haplotyping an ancient double-mutated haplotype 1816delC-1841A in the FOLR1 gene, spread over the whole Eurasian continent, which may be of functional importance for uptake of folate in red blood cells.
dc.publisher0301-4851
dc.relation.ispartofMolecular Biology Reports
dc.sourceMolecular Biology Reports[ISSN 0301-4851],v. 39, p. 4471-4478
dc.subject.otherCancer Incidence
dc.subject.otherFolr1 Gene
dc.subject.otherFolic-Acid
dc.subject.otherIn-Vitro
dc.subject.otherHomocysteine
dc.subject.otherMutations
dc.subject.otherLymphocytes
dc.subject.otherDeterminants
dc.subject.otherMortality
dc.titleA folate receptor alpha double-mutated haplotype 1816delC-1841A is distributed throughout Eurasia and associated with lower erythrocyte folate levels
dc.typeinfo:eu-repo/semantics/Articlees
dc.typeArticlees
dc.identifier.doi10.1007/s11033-011-1236-x
dc.identifier.scopus84863006599-
dc.identifier.isi000301108500127
dc.contributor.authorscopusid7202991775
dc.contributor.authorscopusid32667928200
dc.contributor.authorscopusid57213393602
dc.contributor.authorscopusid8592684900
dc.contributor.authorscopusid35596972100
dc.contributor.authorscopusid6602790170
dc.description.lastpage4478
dc.description.firstpage4471
dc.relation.volume39
dc.type2Artículoes
dc.contributor.daisngid55347
dc.contributor.daisngid6237470
dc.contributor.daisngid565725
dc.contributor.daisngid28836
dc.contributor.daisngid173310
dc.contributor.wosstandardWOS:Nilsson, TK
dc.contributor.wosstandardWOS:Laanpere, M
dc.contributor.wosstandardWOS:Altmae, S
dc.contributor.wosstandardWOS:Serra-Majem, L
dc.contributor.wosstandardWOS:Salumets, A
dc.date.coverdateAbril 2012
dc.identifier.ulpgces
dc.description.sjr0,65
dc.description.jcr2,506
dc.description.sjrqQ2
dc.description.jcrqQ3
dc.description.scieSCIE
item.fulltextSin texto completo-
item.grantfulltextnone-
crisitem.author.deptGIR IUIBS: Nutrición-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Clínicas-
crisitem.author.orcid0000-0002-9658-9061-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameSerra Majem, Luis-
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