当前位置： SCI文献检索 > MOLECULAR BIOLOGY REPORTS期刊下所有文献 > A folate receptor alpha double-mutated haplotype 1816delC-1841A is distributed throughout Eurasia and associated with lower erythrocyte folate levels.

A folate receptor alpha double-mutated haplotype 1816delC-1841A is distributed throughout Eurasia and associated with lower erythrocyte folate levels.

Abstract：

:Folate is crucial for various cellular functions. Several transport mechanisms allow folate to enter the intracellular compartment with folate receptor-α being the major high-affinity receptor. Rare genetic variations in exons of the FR-α 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.

journal_name

Mol Biol Rep

journal_title

Molecular biology reports

authors

Nilsson TK,Laanpere M,Altmäe S,Serra-Majem L,Salumets A

doi

10.1007/s11033-011-1236-x

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

4471-8

issue

eissn

0301-4851

issn

1573-4978

journal_volume

pub_type

杂志文章

在线工具

A folate receptor alpha double-mutated haplotype 1816delC-1841A is distributed throughout Eurasia and associated with lower erythrocyte folate levels.