A nonsense mutation (428G-->A) in the fucosyltransferase FUT2 gene affects the progression of HIV-1 infection.
BACKGROUND
The human FUT2 gene encodes the alpha(1,2)fucosyltransferase that determines secretor status. Homozygous for the nonsense mutation are called non-secretors and are unable to express histo-blood group antigens in secretions and on mucosal surfaces. In this study we have investigated the importance of the FUT2 fucosyltransferase activity on the progress of HIV-1 infection.


METHODS
Swedish blood donors (n = 276), 15 long-term non-progressors (LTNP) and 19 progressors were genotyped with respect to the nonsense mutation 428G-->A in the FUT2 gene. In addition 265/276 blood donors and 19 progressors with rapid or expected progression rate were Delta32 CCR5 genotyped.


RESULTS
Of 276 blood donors 218 (79%) were found to be secretor positive (se+), either homozygous (se+/+) wild type (30%) or heterozygous (se+/-) (49%) and 58 (21%) were homozygous non-secretors (se-/-). Five LTNP (33%) were found to be secretor-positive (se+/+, se+/-) and 10 (67%) se-/-. Of the 19 individuals with normal HIV-1 progression 15 (79 %) were found to be secretor positive and four (21%) were non-secretors. No frequency differences were found in the Delta32 CCR5 allele among the groups studied.


CONCLUSIONS
Strong association (P < 0.001) was observed between the nonsense mutation 428G-->A in the FUT2 gene and a slow disease progression of HIV-1 infection.
Kindberg
Elin
E
Department of Forensic Genetics, National Board of Forensic Medicine, University Hospital, Linköping, Sweden.
Hejdeman
Bo
B
Bratt
Göran
G
Wahren
Britta
B
Lindblom
Bertil
B
Hinkula
Jorma
J
Svensson
Lennart
L
D000328:Adult; D001789:Blood Group Antigens; D018389:Codon, Nonsense; D018450:Disease Progression; D005647:Fucosyltransferases / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000201:enzymology* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D019713:Receptors, CCR5 / Q000235:genetics; D017741:Survivors; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D001789:Blood Group Antigens; D018389:Codon, Nonsense; D005647:Fucosyltransferases; D019713:Receptors, CCR5; D000097631:Galactoside 2-alpha-L-fucosyltransferase