Functional effects of the ABO locus polymorphism on plasma levels of von Willebrand factor, factor VIII, and activated partial thromboplastin time

Lower levels of factor VIII and von Willebrand factor (VWF) have been repor ted in individuals with blood type O compared with individuals with other A BO blood types. However, this relationship has been demonstrated only by as sociation studies and not by linkage studies. Also, it is not clear whether the ABO locus exerts a functional effect directly on these plasma factors or whether the ABO locus is in linkage disequilibrium with another locus th at controls these factors. To distinguish between these 2 possibilities, we applied new statistical methods combining linkage and association tests in a pedigree-based sample. In contrast to most previous studies that used th e ABO phenotypes, our study used the ABO genotypes, permitting us to distin guish AO from AA and BO from BE. Our results clearly showed significant lin kage between the ABO locus and vWF antigen (P=0.00075). In addition, factor VIII coagulant activity and activated partial thromboplastin time showed s uggestive linkage with the ABO locus (P=0.10 and P=0.13). All 3 plasma phen otypes showed significant differences between OO and non-GO genotypes. in a ddition, VWF antigen exhibited significant differences between O heterozygo tes and non-GO homozygotes. This study is unique because ii used a combined linkage and association test, which indicated that the ABO locus itself ha s a functional effect on these plasma phenotypes.