Polymorphism of alpha2 integrin (C807T) is shown to be associated with an increased incidence of thrombotic cardiovascular events. However, it is not clear whether this polymorphism is associated with atherosclerotic arterial wall thickening. In this study, we examined the association of C807T polymorphism with arterial wall thickness in 265 control subjects and 272 patients with type 2 diabetes. In all subjects, intima-media thickness of the right carotid artery in the 807TT group (0.649 +/- 0.028 mm [SE]) was significantly (P = 0.0228, Scheffe's F test) less than in the 807CC group (0.767 +/- 0.033). This effect of polymorphism is gene dose dependent (P = 0.0227, ANOVA). The similar association was also observed in patients with diabetes but not in control subjects. Multiple regression analysis in all subjects revealed that the T allele was inversely (beta = -0.095, P = 0.021) associated with intima-media thickness independent of age, HbA(1c), and HDL cholesterol. Finally, an inverse relation between the occurrence of carotid plaque and the T allele was observed in patients with diabetes with an adjusted odds ratio of 0.487 (P = 0.031) in multiple logistic regression analyses. These results suggest that the number of 807T alleles in alpha2 integrin is protective against atherosclerotic arterial wall thickening and the occurrence of plaque in patients with type 2 diabetes.