Fucosyltransferase 3 polymorphism and atherothrombotic disease in the Framingham Offspring Study.
BACKGROUND
Previous studies have suggested a positive association between phenotypes of fucosyltransferase 3 (FUT3) gene (also known as Lewis gene) and coronary heart disease.


METHODS
We used data on 1735 unrelated subjects in the Framingham Offspring Study to assess whether 3 functional single-nucleotide polymorphisms (SNPs) of the FUT3 gene (T59G, T1067A, and T202C) were associated with prevalent atherothrombotic disease.


RESULTS
Contrary to T1067A and T202C SNPs, there was evidence for an association between T59G SNP and atherothrombotic disease prevalence. In a multivariable model controlling for age, sex, alcohol intake, pack-years of smoking, ratio of total to high-density lipoprotein cholesterol, and diabetes mellitus, ORs (95% CI) for prevalent atherothrombotic disease were 1.0 (reference), 0.80 (0.46-1.41), and 6.70 (1.95-23.01) for TT, TG, and GG genotypes of the T59G SNP, respectively. Minor alleles of T202C and T1067A SNPs showed a modest and nonsignificant association with atherothrombotic disease. Overall, FUT3 polymorphism that influences the enzyme activity (GG genotype for T59G or > or = 1 minor allele of T202C or T1067A) was associated with increased atherothrombotic disease prevalence (OR 1.57, 1.05-2.34), and this association was stronger among abstainers (2-fold increased odds) than among current drinkers (P for interaction .11).


CONCLUSIONS
Our data suggest that functional mutations of the FUT3 gene may be associated with an increased atherothrombotic disease prevalence, especially among abstainers. Additional studies are warranted to confirm these findings.
Djoussé
Luc
L
Division of Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. ldjousse@rics.bwh.harvard.edu
Karamohamed
Samer
S
Herbert
Alan G
AG
D'Agostino
Ralph B
RB
Cupples
L Adrienne
LA
Ellison
R Curtis
RC
D050197:Atherosclerosis / Q000235:genetics*; D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000235:genetics*
D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase