120 S. Nomura et al. Table 4. Genotype frequencies of the six major HPAs Genotype HPA-1a/1a (PlA1/PlA1) HPA-1a/1b (PlA1/PlA2) HPA-1b/1b (PlA2/PlA2) HPA-2a/2a (Kob/Kob) HPA-2a/2b (Kob/Koa) HPA-2b/2b (Koa/Koa) HPA-3a/3a (Baka/Baka) HPA-3a/3b (Baka/Bakb) HPA-3b/3b (Bakb/Bakb) HPA-4a/4a (Pena/Pena) HPA-4a/4b (Pena/Penb) HPA-4b/4b (Penb/Penb) HPA-5a/5a (Brb/Brb) HPA-5a/5b (Brb/Bra) HPA-5b/5b (Bra/Bra) HPA-6a/6a (Caa/Caa) HPA-6a/6b (Caa/Cab) HPA-6b/6b (Cab/Cab) Healthy controls ASO (–) n = 129 n = 76 100 (%) 100 (%) 0 0 0 0 73.6 84.2 23.3 14.5 3.1 1.3 34.9 26.3 51.2 57.9 14.0 15.8 98.4 97.4 1.6 2.6 0 0 93.0 98.7 7.0 1.3* 0 0 96.9 96.1 3.1 3.9 0 0 Type 2 DM Non-diabetic ASO (+) n = 28 ASO n = 17 100 (%) 100 (%) 0 0 0 0 82.1 82.4 17.9 17.6 0 0 35.7 35.3 46.4 41.2 17.9 23.5 96.4 94.1 3.6 5.9 0 0 100 100 0** 0*** 0 0 96.4 100 3.6 0 0 0 * P < 0.05 (χ2 = 5.625); ** P < 0.05 (χ2 = 4.492); *** P < 0.05 (χ2 = 4.314). 1998). Thus, the analysis of HLA antigens and alleles appears to offer some guidelines for the treatment of autoimmune diseases. In the present study, HLA DRB1*1501 was found to be more common in diabetic, particularly ASO-positive, patients. In addition, this allele was also found to be more common in non-diabetic ASO- positive patients. Thus, the association between patients and DRB1*1501 is not always related to type 2 diabetes, because this association is detected in non-diabetic patients. Type 1 diabetes was reported to be associated with some HLA alleles (Park, 2004). However, for the type 2 allele, such relationship was not detected. On the other hand, the association between HLA and infection is possible to detect. In the recent study, Veneri et al. (2005) reported the relationship between Helicobacter pylori and HLA in immune thrombocytopenic purpura patients. Our ﬁndings suggest the hypothesis that HLA regulates immu- noreactive inﬂammation or infection associated with type 2 diabetes or ASO. Thus, analysis of some HLA alleles may provide the information for predicting ASO or type 2 diabetes, if racial differences are taken into account. Diamantopoulos et al. (2002) evaluated 197 patients with type 2 diabetes, and found a signiﬁcant association between HLA-A3 and carotid intimal media thickness. In the Japanese population, the frequency of HLA-A3 is extremely low. In addition, most DRB1*1501 are associ- ated with HLA-A2, -A24 or -A26. The discrepancy between our results and Diamontopoulos’s is thought to depend on racial differences. However, most autoimmune diseases share pathogenetic mechanisms characterized by association with an HLA class II haplotype. Also, the pathogenesis of diabetic or non-diabetic ASO may be heterogeneous; therefore, analysis of a larger population with diverse genetic backgrounds will be needed. FcγRIIIb is a glycosylphosphatidylinositol-anchored protein expressed on neutrophils (Ravetch & Perussia, 1989). NA1 and NA2 located on the neutrophil receptor FcγRIIIb are known to be involved in disorders such as neonatal alloimmune neutropenia, autoimmune neutro- penia and transfusion-related acute lung injury (Lalezari et al., 1960, 1975; Yomtovian et al., 1984). In addition, polymorphisms inﬂuencing the binding afﬁnity between the FcγRs and IgG of different subclasses are recently thought to be important for individual susceptibility to infection with gram-negative bacteria contributing to per- iodontal disease (Meisel et al., 2001). Indeed, Kobayashi et al. (2000) reported the importance of the FcγRIIIb- NA2 allele for susceptibility to IgG in Japanese periodon- titis patients. In the present study, the frequency of NA2/ NA2 was found to be signiﬁcantly higher in ASO-positive type 2 diabetes and non-diabetic ASO patients than in controls. Our results suggest the importance of the NA2 allele in susceptibility to ASO. Apart from some reports of periodontal disease, Fijen et al. (2000) reported that the FcγRIIIb-NA2/NA2 allotype appeared associated with meningococcal disease. However, previous reports have not always noted the importance of the NA2 allele. For example, Raknes et al. (1998) reported that myasthenia gravis patients with the NA1/NA1 genotype had the most severe condition. The function of FcγRIIIb is not entirely clear; however, interestingly, FcγRIIIb induces actin ﬁla- ment assembly that is a prerequisite for phagocytosis, while cross-linking of the FcγRIIIb by immune complexes enhances FcγRII mediated phagocytosis (Salmon et al., 1991; Flesch et al., 1998). These functions may be related to the development of atherosclerosis, since the pathogen- esis of atherosclerosis includes inﬂammation. In addition, our results possibly reﬂect on such a hypothesis. HPA plays an important role in provoking neonatal alloimmune thrombocytopenic purpura, post-transfusion purpura and refractoriness to platelet transfusion. To date, 10 HPA systems have been described and several additional alloantigen systems have been reported (Bussel et al., 2000; Kunicki, 2000, 2002). In particular, HPA-1 (PlA.), HPA-2 (Ko), HPA-3 (Bak), HPA-4 (Pen) and HPA- 5 (Br) have been well established by serological analysis (Kunicki & Newman, 1992). The HPA-1a (PlA1, Zw a ) antigen is by far the most common antigen implicated in neonatal alloimmune thrombocytopenia in a Caucasian population (Taaning et al., 1983; McFarland et al., 1989; Mueller-Eckhardt et al., 1989). On the other hand, HPA- 4b is responsible for neonatal alloimmune thrombocyto- penia in Japanese. This discrepancy in ﬁndings would have occurred because the HPA phenotype frequency varies between races. HPA systems also reside on functional platelet receptor proteins. It has been shown by a number of groups that all platelet-speciﬁc alloantigens thus far dis- covered are located on four platelet membrane GPs: GPIIb, GPIIIa, GPIb and GPIa. Thus, it has been reported that polymorphism of HPA is a genetic risk factor for thrombotic diseases (Weiss et al., 1996; Gonzalez- Conejero et al., 1998; Sperr et al., 1998; Carter et al., 1999; Kroll et al., 2000; Baker et al., 2001; Mikkelsson et al., © 2006 The Authors Journal compilation © 2006 Blackwell Publishing Ltd, International Journal of Immunogenetics 33, 117–122