Infection-associated FUT2 (Fucosyltransferase 2) genetic variation and impact on functionality assessed by in vivo studies

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Lara M Silva (Author) Other; Ana S Carvalho (Author) Other; Patrice Guillon (Author) Other; Susana Seixas (Author) Other; Maria Azevedo (Author) Other; Raquel Almeida (Author) FMUP; Nathalie Ruvoen Clouet (Author) Other; Celso A Reis (Author) FEUP; Jacques Le Pendu (Author) Other; Jorge Rocha (Author) FCUP; Leonor David (Author) FMUP

Journal

Title: Glycoconjugate Journal

Vol. 27

Pages: 61-68

ISSN: 0282-0080

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 26 Citations

Scopus - 26 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-003-B23

DOI: 10.1007/s10719-009-9255-8

Abstract (EN): The secretor (Se)/nonsecretor (se) histo-blood group variation depends on the action of the FUT2 enzyme and has major implications for human susceptibility to infections. To characterize the functionality of FUT2 variants, we assessed the correlation between saliva phenotypes and sequence variation at the FUT2 gene in sixty seven individuals from northern Portugal. While most non-secretor haplotypes were found to carry the 428G > A nonsense mutation in association with a 739G > A missense substitution, we have also identified a recombinant haplotype carrying the 739*A allele together with the efficient 428*G variant in individuals with the Se phenotype. This finding suggested, in contrast to previous results, that the 739*A allele encodes an efficient Se allele. To test this hypothesis we evaluated the in vivo enzyme activity of full coding expression constructs in transient transfection of CHO-K1 cells using FACS (fluorescence-activated cell sorting) analysis and expression of type 2 and type 3 chain H structures as read out. We detected FUT2 activity for the 739*A expression construct, demonstrating that the 739G > A substitution is indeed not inactivating. In accordance with the hypothesis that FUT2 is under long standing balancing selection, we estimated that the time depth of FUT2 global genetic variation is as old as 3 million years. Age estimates of specific variants suggest that the 428G > A mutation occurred at least 1.87 million years ago while the 739G > A substitution is about 816,000 years old. The 385A > T missense mutation underlying the non-secretor phenotype in East Asians appears to be more recent and is likely to have occurred about 256,000 years ago.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8