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

. Salomaa V, Pankow J, Heiss G, Cakir B, Eckfeldt JH, Ellison RC, Myers RH, Hiller KM, Brantley KR, Morris TL, Weston BW (National Public Health Institute, Helsinki, Finland, University of North Carolina, University of Minnesota, Boston University School of Medicine, USA). Genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI Family Heart Study, J Intern Med 2000; 247: 689–698. Objectives. To examine the prevalence of four mutations, T59G, T1067A, T202C and C314T, of the human α(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst persons with Lewis negative and those with Lewis positive blood group phenotype. An additional objective was to explore the hypothesis that these mutations are associated with coronary heart disease and inflammatory reaction. Design. A population‐based cross‐sectional study. Setting. Analysis of samples and data from the National Heart Lung and Blood Institute Family Heart Study. Subjects. All Lewis (a–b–) participants (n = 136) and a sample of Lewis positive participants (n = 136) of the Family Heart Study; all were of Caucasian ethnicity. Main outcome measures. The prevalence of examined mutations by Lewis phenotype. Results. The examined mutations were common and strongly associated with the Lewis (a–b–) phenotype. Accordingly, 90–95% of Lewis (a–b–) individuals amongst Caucasians can be identified by screening for these four mutations. Exploratory analyses suggested that with the exception of T59G, all examined mutations were positively associated with prevalent coronary heart disease, although not statistically significantly, perhaps due to the small number of prevalent coronary heart disease cases. C‐reactive protein tended to be 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 responsible for the vast majority of Lewis (a–b–) phenotypes in Caucasians. These mutations are common in the population at large and may be associated with increased risk of coronary heart disease. Further studies using larger samples are warranted.