Racial and genetic determinants of plasma factor XIII activity

Factor XIII (F XIII), a plasma transglutaminase, is essential for normal he mostasis and fibrinolysis. Plasma F XIII consists of two catalytic A (F XII IA) and two non-catalytic B (F XIIIB) subunits. Activated F XIII is involve d in the formation of fibrin gel by covalently crosslinking fibrin monomers . As the characteristics of the fibrin gel structure have been shown to be associated with the risk of coronary heart disease (CHD), F XIII activity m ay play a seminal role in its etiology. In this investigation, we determine d plasma F XIII activity in two racial groups, including Asian Indians (n = 258) and Chinese (n = 385). Adjusted plasma F XIII activity was significan tly higher in Indian men (142 vs. 110%; P < 0.0001) and women (158 vs. 111% ; P < 0.0001) than their Chinese counterparts. As compared to Indians where the distribution of F XIII activity was almost normal, in Chinese it was s kewed towards low activity. In both racial groups, bivariate and multivaria te analyses showed strong correlation of F XIII activity with plasma fibrin ogen and plasminogen levels. Race explained about 25% of the variation in F XIII activity even after the adjustment of significant correlates. We also determined the contribution of common genetic polymorphisms in the F XIIIA and F XIIIB genes in affecting plasma F XIII activity. Both loci showed si gnificant and independent effects on plasma F XIII activity in Indians (F X IIIA, P < 0.01; F XIIIB, P < 0.05) and Chinese (F XIIIA, P < 0.0001: F XIII B. P < 0.13) in a gene dosage fashion. This study shows that both racial an d genetic components play a significant role in determining plasma F XIII a ctivity, and consequently it may affect the quantitative risk of CHD. (C) 2 000 Wiley-Liss, Inc.