Genetic variation of FUT3 in Ghanaians, Caucasians, and Mongolians.
BACKGROUND
The FUT3 gene regulates the expression of Lewis blood group antigens. Several lines of evidence suggest association between expression of these antigens and Helicobacter pylori infection or susceptibility to cardiovascular diseases. Single-nucleotide polymorphisms (SNPs) responsible for the Lewis-negative phenotype have been reported, but systematic sequence analyses have not yet been performed.


METHODS
The polymerase chain reaction product containing the whole FUT3 coding region (1086 bp) was sequenced in three human populations, Ghanaians (n = 106), Caucasians (n = 100), and Mongolians (n = 50). Some haplotypes were determined by sequencing cloned inserts, and the other haplotypes were inferred by the free software program PHASE. Also examined was the functional significance of several newly identified SNPs by a transient expression study.


RESULTS
Thirty-two SNPs were found, including 15 novel SNPs, in the three populations. The functional impact of three nonsynonymous SNPs that occurred on the Lewis-positive alleles or weakly enzyme-inactivating alleles was examined. A transient expression study suggested that 478C>T and 968G>C are enzyme-inactivating mutations.


CONCLUSIONS
Sequence analysis identified many SNPs, but most of them are in complete linkage disequilibrium with previously reported SNPs responsible for the Lewis-negative phenotype. 13G>A, 59T>G, and 202T>C seem to be useful as tag SNPs for detection of Lewis-negative alleles in genotyping of Lewis blood groups and large-scale association studies with diseases in many populations.
Soejima
Mikiko
M
Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Munkhtulga
Lkhagvasuren
L
Iwamoto
Sadahiko
S
Koda
Yoshiro
Y
D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D004252:DNA Mutational Analysis; D005647:Fucosyltransferases / Q000235:genetics*; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000235:genetics; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics*; D044465:White People / Q000235:genetics
D007983:Lewis Blood Group Antigens; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase