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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2024.)
© 2000 American Heart Association, Inc.

Thrombosis

Functional Effects of the ABO Locus Polymorphism on Plasma Levels of von Willebrand Factor, Factor VIII, and Activated Partial Thromboplastin Time

Juan Carlos Souto; Laura Almasy; Eduardo Muñiz-Diaz; José Manuel Soria; Montserrat Borrell; Laia Bayén; José Mateo; Pedro Madoz; William Stone; John Blangero; Jordi Fontcuberta

From Unitat d’Hemostàsia i Trombosi (J.C.S., J.M.S., M.B., L.B., J.M., J.F.) and Banc de Sang (E.M.-D., P.M.), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; the Department of Genetics (L.A., J.B.), Southwest Foundation for Biomedical Research, San Antonio, Tex; and the Department of Biology (W.S.) Trinity University, San Antonio, Tex.

Abstract—Lower levels of factor VIII and von Willebrand factor (vWF) have been reported in individuals with blood type O compared with individuals with other ABO blood types. However, this relationship has been demonstrated only by association 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 that 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 the ABO phenotypes, our study used the ABO genotypes, permitting us to distinguish AO from AA and BO from BB. Our results clearly showed significant linkage between the ABO locus and vWF antigen (P=0.00075). In addition, factor VIII coagulant activity and activated partial thromboplastin time showed suggestive linkage with the ABO locus (P=0.10 and P=0.13). All 3 plasma phenotypes showed significant differences between OO and non-OO genotypes. In addition, vWF antigen exhibited significant differences between O heterozygotes and non-OO homozygotes. This study is unique because it used a combined linkage and association test, which indicated that the ABO locus itself has a functional effect on these plasma phenotypes.

Key Words: ABO blood group • von Willebrand factor • factor VIII • genetics • functional polymorphism

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