Genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI Family Heart Study

Objectives. To examine the prevalence of four mutations, T59G, T1067A, T202 C and C314T, of the human alpha(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst persons with Lewis negative and those with Lewis positive blood gro up phenotype. An additional objective was to explore the hypothesis that th ese mutations are associated with coronary heart disease and inflammatory r eaction. Design. A population-based cross-sectional study. Setting. Analysis of samples and data from the National Heart Lung and Bloo d Institute Family Heart Study. Subjects. All Lewis (a-b-) participants (n = 136) and a sample of Lewis pos itive participants (n = 136) of the Family Heart Study; all were of Caucasi an ethnicity. Main outcome measures. The prevalence of examined mutations by Lewis phenot ype. Results. The examined mutations were common and strongly associated with th e Lewis (a-b-) phenotype. Accordingly, 90-95% of Lewis (a-b-) individuals a mongst Caucasians can be identified by screening for these four mutations. Exploratory analyses suggested that with the exception of T59G, all examine d mutations were positively associated with prevalent coronary heart diseas e, although not statistically significantly, perhaps due to the small numbe r of prevalent coronary heart disease cases. C-reactive protein tended to b e higher amongst persons with a TC or CC genotype at position 202 (3.07 +/- 0.41 vs. 2.08 +/- 0.32 mg L-1, P = 0.06). Conclusions. Four specific mutations of fucosyltransferase 3 gene are respo nsible for the vast majority of Lewis (a-b-) phenotypes in Caucasians. Thes e mutations are common in the population at large and may be associated wit h increased risk of coronary heart disease. Further studies using larger sa mples are warranted.