doi: 10.1111/j.1744-313X.2006.00581.x Ge Blackwel PublishingnLtdetic analysis of HLA, and HPA typing in type 2 diabetes and ASO S. Nomura,* A. Shouzu,† S. Omoto,† T. Matsuzaki,‡ M. Yamaoka,‡ M. Abe,‡ M. Hosokawa,‡ M. Nishikawa,† T. Iwasaka† & S. Fukuhara* Summary We examined the genetic status of human leucocyte antigens (HLA), human platelet alloantigens (HPA) and neutrophil-speciﬁc antigens (NA) in patients with type 2 diabetes mellitus and diabetic arteriosclerosis obliterans (ASO). To our knowledge, the present study is the ﬁrst report showing the relationship among three genetic factors in type 2 diabetes mellitus and ASO patients. HLA typing was performed by the polymerase chain reaction (PCR)–restriction fragment length polymorphism method. HPA-typing and NA-typing were by a PCR-sequence-speciﬁc primer method. The incidence of HLA-DRB1*1501 was found to be signiﬁcant in type 2 diabetes and non-diabetic, particularly ASO-positive patients, compared to control subjects. There were no differences in NA1/NA2 between the control and diabetic or non-diabetic ASO groups. However, the frequency of NA2/NA2 in ASO-positive diabetes and non-diabetic ASO patients was signiﬁcantly higher than controls. The a/b genotype of HPA-5a/5b was signiﬁcantly lower in type 2 diabetes and non-diabetic ASO-positive patients than in controls. These ﬁndings suggest that genetic studies of HLA, and HPA could be useful to understand the pathogenesis of type 2 diabetes and ASO. Introduction The underlying pathology of atherosclerosis obliterans (ASO) is basically atherosclerosis, and complete occlu- sions by fresh or old thrombi are often observed (Schwartz et al., 1995; Williams & Tabas, 1995). Recent evidence indicates that the incidence of thrombotic Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. * The First Department of Internal Medicine, † The Second Department of Internal Medicine, ‡ Department of Blood Transfusion, Kansai Medical University, Osaka, Japan Received 6 December 2004; revised 11 July 2005; accepted 22 December 2005 Correspondence: Shosaku Nomura, The First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8507, Japan. Tel: + 81 6 6992 1001; Fax: + 81 725 32 1113; E-mail: shosaku-n@mbp.ocn.ne.jp disease is steadily increasing among Asian populations (Kauffmann-Zeh et al., 2000). Epidemiological studies indicate that thrombotic diseases result from complex interactions between susceptibility factors, chronic en- vironmental inﬂuences and established intercurrent dis- orders such as diabetes mellitus (Kunicki, 2002). The critical role of platelets in the thrombotic process is now well accepted (Rauch et al., 2001). At sites of vascular injury, thrombus formation is initiated by binding platelet glyco- protein (GP) Ib to von Willebrand factor and binding platelet GPIa/IIa to collagen, which leads to platelet acti- vation and aggregation by binding platelet GPIIb/IIIa to ﬁbrinogen and von Willebrand factor (Kunicki, 2000). Several polymorphisms in the genes encoding for platelet GPs have been associated with increased platelet ad- hesiveness and aggregation, and in some studies, they have been associated with an increased risk of arterial throm- bosis (Bray, 1999; Bussel et al., 2000; Reiner et al., 2000). Human platelet alloantigens (HPA) are important for sensitization to platelet GP polymorphisms. In general, HPAs play important roles in the pathogenesis of neonatal alloimmune thrombocytopenia and post-transfusion pur- pura, as well as in some cases of refractoriness to platelet transfusion (Von dem Borne Kr. et al., 1981; Von dem Borne Kr. & Ouwehand, 1989; McFarland et al., 1991; Dreyfus et al., 1997). However, there are few reports available concerning the relationship between type 2 dia- betes and diabetic ASO. Leucocytes have been suggested to play an important role in the development of atherosclerosis (Beekhuizen & van Furth, 1993; Jonasson et al., 1986). The ﬁrst step in the process of leucocyte inﬁltration into the sub-endothelial space is adhesion of circulating cells to the endothelium (Jonasson et al., 1986). Thus, the pathogenesis of athero- sclerosis appears to be inﬂammation (Ross, 1993). A recent study suggests genetic predisposition and chronic inﬂam- mation play the leading roles in the early stages and in the development of vascular damage (Diamantopoulos et al., 2002; Tsuchiya et al., 2003). In addition, the Fcγreceptor polymorphism is related to susceptibility of some immu- nological diseases (Dijstelbloem et al., 2000; Nieto et al., 2000; Fujimoto et al., 2001), and neutrophil-speciﬁc anti- gens (NA)1 and NA2 are located on the Fcγreceptor IIIb (Matsuo et al., 2000). On the other hand, studies have long suggested associations between certain human leuco- cyte antigens (HLA) and many autoimmune diseases. © 2006 The Authors Journal compilation © 2006 Blackwell Publishing Ltd, International Journal of Immunogenetics 33, 117–122 117