Assessment of HNA alloimmunisation risk in Northeastern Thais, Burmese and Karen.

OBJECTIVES: This study aimed to determine human neutrophil antigen (HNA) frequency, estimate possible HNA incompatibilities and predict the risk of HNA alloimmunisation in the Northeastern Thai, Burmese and Karen populations. BACKGROUND: Alloantibodies against HNA are implicated in a number of clinical conditions, including immune-mediated neutropenia and transfusion reactions. METHODS: A total of 400 unrelated healthy Thais, 261 Burmese and 249 Karen was included in this study. DNA samples were typed for HNA-1, -3, -4 and -5 systems using polymerase chain reactions with sequence-specific primers (PCR-SSP). RESULTS: In this cohort, HNA-1a was more prevalent than HNA-1b. Accordingly, the possible risk of HNA-1a alloimmunisation against HNA-1a is lower than HNA-1b (0·0802-0·1351 vs 0·2293-0·2497). This is in contrast to the situation reported in Caucasian and African populations. The predicted risk of HNA-3 incompatibility in Thais, Burmese and Karen were 28·09%, 30·66% and 22·77%, respectively. The possible risks of HNA-3a alloimmunisation were 0·0493 in Thais, 0·0608 in Burmese and 0·0196 in Karen, respectively. No individuals were found to be homozygous for HNA-4bb. The probability of developing alloantibodies against HNA-4a was low in these populations and every population in Asia. In contrast, the overall frequency of HNA-5bb homozygous individuals was high in this study, peaking at 0·192. CONCLUSIONS: This is the first study that reported the allele frequencies of HNA-1, -3, -4, and -5 in a large sample of healthy unrelated individuals from ethnic Thais, Burmese and Karen. Our results indicated the high possible risk of HNA-1, -3 and -5 alloimmunisation in these populations.

Human platelet antigens in Burmese, Karen and north-eastern Thais.

OBJECTIVES: A comparative study of allele frequencies at HPA-1 to -6 and HPA-15 in Burmese and Karen populations as well as at HPA-15 in north-eastern Thais (NET) is presented. BACKGROUND: Human platelet antigens (HPAs) are clinically important in several immune platelet disorders, including foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura (PTP) and platelet transfusion refractoriness (PTR). The knowledge of antigen frequencies in a population is essential for the evaluation of patients suffering from immune-mediated platelet disorders. METHODS: A total of 285 unrelated, healthy Burmese, 242 Karen and 300 NET were recruited to this study. Genotype and allele frequencies of HPA-1 to -6 and HPA-15 were defined using polymerase chain reaction sequence-specific primers (PCR-SSP) RESULTS: No individuals homozygous for HPA-1bb, -2bb, -4bb, -5bb and -6bb were detected. HPA-1a, -2a, -4a, -5a and -6a were present in all samples of Burmese and Karen origin. HPA-1b, -2b, -4b, -5b and -6b were rare in these populations. The frequencies of HPA-3a/-3b were 60·4/39·6% in Burmese and 55·8/44·2% in Karen, respectively. Frequencies of HPA-15a/-15b were 57·2/42·8% in Burmese, 52·5/47·5% in Karen and 49·8/50·2% in NET. CONCLUSIONS: The frequencies of HPA genotypes in our study indicates that HPA-1a, -2a, -4a, -5a and -6a are unlikely involved in FNAIT, PTP and PTR in Burmese and Karen populations. However, HPA-1b, -2b, -3a, -3b, -4b, -5b, -6b, -15a and -15b may likely stimulate alloantibodies in these populations.

HLA alleles and haplotypes in Burmese (Myanmarese) and Karen in Thailand.

This is the first report on human leukocyte antigen (HLA) allele and haplotype frequencies at three class I loci and two class II loci in unrelated healthy individuals from two ethnic groups, 170 Burmese and 200 Karen, originally from Burma (Myanmar), but sampled while residing in Thailand. Overall, the HLA allele and haplotype frequencies detected by polymerase chain reaction sequence-specific primer (PCR-SSP) at five loci (A, B, C, DRB1 and DRQB1) at low resolution showed distinct differences between the Burmese and Karen. In Burmese, five HLA-B*15 haplotypes with different HLA-A and HLA-DR/DQ combinations were detected with three of these not previously reported in other Asian populations. The data are important in the fields of anthropology, transplantation and disease-association studies.

Development of a multiplex polymerase chain reaction-sequence-specific primer method for NKG2D and NKG2F single-nucleotide polymorphism typing using isothermal multiple displacement amplification products.

Natural killer group 2 member D (NKG2D) on immune effector cells recognizes multiple stress-inducible ligands. NKG2D single-nucleotide polymorphism (SNP) haplotypes were related to the levels of cytotoxic activity of peripheral blood mononuclear cells. Indeed, these polymorphisms were also located in NKG2F. Isothermal multiple displacement amplification (IMDA) is used for whole genome amplification (WGA) that can amplify very small genomic DNA templates into microgram with whole genome coverage. This is particularly useful in the cases of limited amount of valuable DNA samples requiring multi-locus genotyping. In this study, we evaluated the quality and applicability of IMDA to genetic studies in terms of sensitivity, efficiency of IMDA re-amplification and stability of IMDA products. The smallest amount of DNA to be effectively amplified by IMDA was 200 pg yielding final DNA of approximately 16 µg within 1.5 h. IMDA could be re-amplified only once (second round of amplification), and could be kept for 5 months at 4°C and more than a year at -20°C without loosing genome coverage. The amplified products were used successfully to setup a multiplex polymerase chain reaction-sequence-specific primer for SNP typing of the NKG2D/F genes. The NKG2D/F multiplex polymerase chain reaction (PCR) contained six PCR mixtures for detecting 10 selected SNPs, including 8 NKG2D/F SNP haplotypes and 2 additional NKG2D coding SNPs. This typing procedure will be applicable in both clinical and research laboratories. Thus, our data provide useful information and limitations for utilization of genome-wide amplification using IMDA and its application for multiplex NKG2D/F typing.

Linkage disequilibrium of polymorphic RAET1 genes in Thais.

Retinoic acid early transcripts-1 (RAET1) or unique long 16 (UL-16) binding proteins (ULBPs) is a gene cluster encoding for molecules acting as ligands to natural killer group 2 D (NKG2D), a receptor expressed on immune cells. Binding of these ligands to the receptor activates immune cells leading to killing of tumor cells and also viral-infected cells. The information on polymorphism of RAET1 is limited. In this report, we analyze the linkages between four polymorphic RAET1 genes: RAET1E, RAET1G, RAET1H and RAET1L, in 318 unrelated Thais. The strongest linkage disequilibrium was found between RAET1E and RAET1G, with P-value, D' and r(2) of <5.0 x 10(-5), 0.707 and 0.840, respectively. RAET1E(*)001 was found to be in linkage disequilibrium with RAET1G(*)002, and RAET1E(*)002 with RAET1G(*)001. Evidently, there were possible RAET1 haplotypes with haplotype frequencies of more than 10% consisting of RAET1E(*)001; RAET1G(*)002; RAET1H(*)001; RAET1L(*)001 and RAET1E(*)002; RAET1G(*)001; RAET1H(*)002; RAET1L(*)003. This study provides basic information on polymorphisms of RAET1 and possible RAET1 haplotypes in Thais.

HLA class I and II alleles and haplotypes in ethnic Northeast Thais.

Allele frequencies (AFs) and haplotypic associations of human leukocyte antigen (HLA) class I and II were investigated in 400 unrelated, healthy, ethnic Northeast Thais. HLA-A, -B, -Cw, -DRB1 and -DQB1 were typed by polymerase chain reaction-sequence specific primer, -sequence specific oligonucleotide probe and -single-strand conformation polymorphism methods. In this population, 17 HLA-A, 26 HLA-B, 15 HLA-Cw, 26 HLA-DRB1 and 13 HLA-DQB1 alleles (or groups of alleles) were found. AFs > 10% included A*11 (23.3%), 24 (18.8%), 0207 (14.4%), 33 (11.5%), 0203 (10.6%); B*4601 (13.9%); Cw*07(01-03) (18.5%), 01 (15.9%), 04 (12.0%), 0304 (10.6%); DRB1*1502 (18.5%), 1202 (13.4%); DQB1*0502 (20.3%), 0501 (16.3%), 0301 (14.1%) and 02 (10.9%). The most common of 2-locus haplotypes included A*0207-B*4601 (9.3%), B*4601-Cw*01 (13.5%), B*5801-DRB1*0301 (5.8%) and DRB1*1502-DQB1*0501 (14.1%). Of the 49 five-locus HLA haplotypes identified, 24 were confirmed in 31 family studies: the most common being; A*33-Cw*0302-B*5801-DRB1*0301-DQB1*02 (4.6%), A*0207-Cw*01-B*4601-DRB1*09-DQB1*0303 (3.4%) and A*33-Cw*07(01-03)-B*44-DRB1*07-DQB1*02 (2.6%). Apparently, the HLA-B*46-carrying haplotype is fragmented in ethnic Northeast Thais, including seven haplotypes with different HLA-A and HLA-DR/DQ combinations. One of these haplotypes (A*11-Cw*01-B*4601-DRB1*1202-DQB1*0502) has not been reported in other Asians. The results indicated that there were marked differences in the distribution of HLA alleles and haplotypes between ethnic Northeast Thais and other ethnic groups in Southeast and East Asia. These results also dictate that future studies of HLA alleles and diseases need precise identification of ethnically and geographically matched controls. The HLA allele and haplotype analyses in this large sample provide baseline information on ethnic Northeast Thais for anthropological studies and for determining HLA allele/haplotype frequencies when searching for HLA-compatible donors for unrelated bone marrow transplantation.

HLA-B*27 subtypes in Northern and Northeastern Thais, Karens, and Bamars determined by a high-resolution PCR-SSP technique.

Human leukocyte antigens (HLA), class I, are a group of antigens expressed on most nucleated cell surfaces. They transport endogenous peptides to the cell surface for recognition by T-cell receptors. Their functions are involved in immune responses. Many diseases are associated with HLA alleles, especially HLA-B*27 that is strongly associated with ankylosing spondylitis (AS). HLA-B*27 consists of 42 subtypes. Different subtypes of HLA-B*27 were reported in different ethnic groups of AS patients. In this study, a high-resolution polymerase chain reaction-sequence-specific primer technique has been developed to define all the HLA-B*27 subtypes with a total of 29 primer mixtures. Two of the primer mixes were used to detect the HLA-B*27-specific group, and 27 primer mixes were used to identify 42 subtypes (B*2701-B*2721 and B*2723-B*2743). The HLA-B*27-group-specific primers have been tested in unrelated healthy subjects; 846 Northeastern Thais (NET), 334 Northern Thais (NT), 264 Karens, and 310 Bamars. Sixty-three NET (phenotype frequency, PF = 7.4%), 24 NT (PF = 7.1%), 5 Karens (PF = 1.8%), and 12 Bamars (PF = 3.9%) were positive for HLA-B*27. Only B*2704 was found in Karens, whereas B*2704, B*2705/37/39, B*2706, and B*2707 were found in NET and NT. In Bamars, B*2704, B*2705/37/39, B*2706, and B*2725 were found. The distribution of HLA-B*27 subtypes was compared with other studies in Asian and Caucasian populations. Significant differences of the distribution of HLA-B*27 subtypes were found in most of the populations. This study established a simple technology for HLA-B*27 subtyping and provided basic information for anthropology and further studies in disease associations.

Associations of MICB with cervical cancer in north-eastern Thais: identification of major histocompatibility complex class I chain-related gene B motifs influencing natural killer cell activation.

The expression of MICB, a member of the major histocompatibility complex class I chain-related gene B family, is induced in response to cellular stress. It is one of the ligands to the NKG2D receptor. MICB is polymorphic, but the distribution of MICB polymorphism in north-eastern Thais and their potential associations with cancer have not yet been elucidated. In this study, polymerase chain reaction-sequence-specific primers were developed to identify 15 MICB alleles and one group of alleles. We performed MICB typing in 100 healthy north-eastern Thai females (NETF) and 99 cervical cancer patients to evaluate the association of MICB polymorphisms and the risk of developing cervical cancer. Eight and nine alleles were detected in the NETF and cervical cancer respectively. MICB*00502 was associated negatively with a corrected P-value of 0.0009, suggesting the existence of a protective allele in cervical cancer. Amino acid substitutions carried by this allele were investigated for their potential involvement in natural killer (NK) cell activation. Although lysine at amino acid position 80 (Lys80) and aspartic acid at position 136 (Asp136) were associated negatively with cervical cancer, only MICB carrying Asp136 could induce NK cell killing more efficiently than MICB-Lys80 when the NK cells were blocked by anti-NKG2D. This result suggested that aspartic acid at position 136 may affect NKG2D binding, leading to different degrees of immune cell activation.

MICA, MICB, and MHC beta block matching in bone marrow transplantation: relevance to transplantation outcome.

Genetic testing of the MHC is required for selection of donors for bone marrow transplantation. The outcome of related bone marrow transplantation is usually superior to that of unrelated bone marrow transplantation. This may be the result of inaccurate or incomplete genetic testing employed for selection of donor for transplantation. Based on MHC haplotype matching, MHC block matching has been developed for selection of potential unrelated donor. Block matching has been shown previously to improve outcome when added to the conventional method of human leukocyte antigen (HLA) typing for selection of donors. In this study, we have retrospectively analyzed 44 donor recipient pairs from the Australian Bone Marrow Donor Registry Repository with respect to matching of HLA-B and HLA-Cw by sequence-based typing and MICA and MICB by polymerase chain reaction-sequence specific primer and MHC beta block matching and correlated these results with survival. Beta block matching was correlated with MIC matching (p < 0.005) and with HLA-B and HLA-Cw matching. Patients who were HLA-B and -Cw matched had significantly improved survival when they were additionally matched for MHC beta block (p(c) = 0.04) or MIC (p(c) = 0.05).

Genotyping of human platelet antigens in ethnic Northeastern Thais by the polymerase chain reaction-sequence specific primer technique.

Human platelet antigens (HPA) are important in neonatal alloimmune thrombocytopenia (NAITP), post-transfusion purpura (PTP), refractoriness to platelet transfusion therapy and population genetics. The distribution of HPA in a Northeast Thai population was studied. 300 healthy, unrelated, and ethnic Northeastern Thais were randomly selected. Using the polymerase chain reaction-sequence specific primer technique (PCR-SSP), the frequency of HPA-1, -2, -3, -4, -5 and -6 were determined. The phenotype frequencies were 100 per cent for HPA-1a, 4a, 5a, and 6a. For HPA-1b, 2a, 2b, 3a, 3b, 5b and 6b, the frequencies were 5.7, 99.7, 12.3, 78.0, 71.3, 7.3 and 3.0 per cent, respectively. The HPA-4b was not found. The HPA frequencies in our subjects were quite similar to other Asian populations but were different from Caucasians. The distribution of HPA genotypes encountered in our study indicate that HPA-1a, -4a, -4b, -5a and -6a will not be involved in NAITP, PTP and refractoriness to platelet transfusion therapy in Northeastern Thais. Moreover, HPA-1b, -2a, -2b, -3a, -3b, -5b and -6b may induce alloantibodies in these patients.

Anti-P1: the most common unexpected antibodies in northeastern-Thais.

The prevalence of unexpected antibodies in the Northeastern-Thai population was studied. Sera were collected from 25,673 blood donors including 18,209 males and 7,464 females. The sera were screened for unexpected antibodies by saline and enzyme techniques. The sera which gave a positive antibody screening test were identified for specificity of antibody. The result demonstrated that 3,928 from 25,673 samples (15.30%) were positive for the antibody screening test and only 3,883 samples could be identified for specificity of antibody. The most common unexpected antibodies were anti-P1, anti-lewis and anti-P1 + anti-lewis with the frequency of 70.8, 18.6 and 10.1 per cent, respectively. The prevalence of anti-P1 in this study was higher than that reported in Central Thailand and Southeast Asia which may due to the high prevalence of liver fluke infection in the Northeastern-Thai population.

Association of polymorphic extracellular domains of MICA with cervical cancer in northeastern Thai population.

Cancer of the cervix is one of the common cancers among women worldwide. The primary risk factor of cervical cancer is the high-risk group human papillomavirus infection. Host genetic factors should also be involved. Major histocompatibility complex class I chain related A (MICA), a ligand to the natural killer cell receptor group (NKG)2D receptor relevant to immune surveillance, was investigated as a potential candidate. MICA is highly polymorphic. Although the data were limited regarding functional polymorphism, it is conceivable that polymorphism of MICA may contribute to different degree of immune activation caused by different NKG2D-binding affinity, acting as a susceptible factor for development of cervical cancer. In this study, we have developed a polymerase chain reaction-sequence-specific primer technique defining most of MICA alleles with a total of 41 primer mixes. This set of primers could especially discriminate MICA*045 (formerly 052), a common allele in northeastern Thai population, from MICA*00701, a common allele in Caucasian population. Based on the distribution of MICA in northeastern Thai population, only 27 primer mixes were required to screen the MICA polymorphisms in this population. This set of primers was used for MICA typing of 100 samples of cervical cancer compared with 94 samples of healthy northeastern Thai females (NETF). Thirteen alleles or groups of alleles were identified in these samples. Common alleles in our population were MICA*00801(027,048)/0803, MICA*010 and MICA*00201(020, 023, 050)/30/41. Statistically significant differences were not observed in the distributions of MICA alleles between different stages of patients and the control group. However, there were particular residues that were negatively associated with cervical cancer, suggesting active MICA motifs in immune activation.

Polymorphic Alu insertions and their associations with MHC class I alleles and haplotypes in the northeastern Thais.

Polymorphic Alu insertions (POALINs) are known to contribute to the strong polymorphic nature of the Major Histocompatibility Complex (MHC). Previous population studies on MHC POALINs were limited to only Australian Caucasians and Japanese. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA-A and -B associations, and the three and four locus alpha block POALIN haplotype frequencies in the Northeastern (NE) Thai population. Of the five POALINs, the lowest frequency was 0.018 for AluyHF and the highest frequency was 0.292 for AluyHJ and AluyHG. The strongest positive associations between the POALINs and HLA class I alleles was between AluyMICB and HLA-B*57, AluyHJ and HLA-A*24 and HLA-A*01, and AluyHG and HLA-A*02, supporting previous findings in Caucasians and Japanese. Single POALIN haplotypes were found more frequently than multiple POALIN haplotypes. However, of the seven different POALIN haplotypes within the MHC alpha block, there were only two significant differences between the NE Thais, Caucasians and Japanese. This study confirms that the MHC POALINs are in linkage disequilibrium with HLA-A and -B alleles and that there are significant frequency differences for some of the POALINs when compared between NE Thai, Caucasians and Japanese.

HLA-B*15 subtypes in the population of north-eastern Thailand.

The HLA-B*15 group is the most polymorphic HLA-B allele and so has several subtypes. These subtypes have not been defined in the population of north-eastern Thailand (NET). In a previous study, using polymerase chain reaction-sequence-specific primers (PCR-SSP), subtypes were categorized into four groups, namely: group I: HLA-B*15 (01, 04-07, 12, 14, 19, 20, 24, 25, 26N, 27, 32, 33, 34 and 35); group II: HLA-B*15 (02, 08, 11, 15, 28 and 30); group III: HLA-B*1503/4802; group IV: HLA-B*1521. Groups I and II occurred frequently (allele frequency = 8.0 and 2.5%), and thus we optimized the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) method to identify HLA-B*15 subtypes of groups I and II. Eighty samples of DNA carrying HLA-B*15 from 300 healthy unrelated individuals were tested. B*1502 (52.5%) and B*1525 (13.8%) were the most common subtypes found in NET. They also showed strong linkage disequilibrium with HLA-Cw and heterogeneity of HLA-A, DR, DQ haplotypes. Although limited conclusions can be drawn from this study because of the small number of DNA references used, the baseline data will be useful in the selection of common HLA-B*15 alleles when subtyping for unrelated donor transplantations.

Major histocompatibility complex class I chain-related gene A in Thai psoriasis patients: MICA association as a part of human leukocyte antigen-B-Cw haplotypes.

Psoriasis is a chronic inflammatory skin disorder. Although the aetiology and pathogenesis of psoriasis are unproven, it is hypothesised that the major histocompatibility complex (MHC) gene/haplotype contributes to the susceptibility of psoriasis in many populations. MHC class I chain-related gene A (MICA), located 46-kb centromeric of HLA-B, is expressed on keratinocytes and fibroblasts. MICA is in linkage disequilibrium with HLA-B and is involved in natural killer-cell functions. To investigate the relative contribution of the MICA gene in the pathogenesis of psoriasis, extracellular polymorphisms of MICA were studied by polymerase chain reaction-sequence specific primers in 128 Thai psoriasis patients (87 and 41 were Types I and II, respectively) from Srinagarind Hospital, Faculty of Medicine, Khon Kaen University. The control group included 255 healthy, unrelated Northeast Thais. We observed 11 MICA alleles (or groups of alleles) in the patients. A comparison of the psoriasis patients and the control group revealed that MICA*010 and MICA*017 were associated with Type I psoriasis whereas only MICA*010 was associated with Type II. The haplotype analysis revealed that MICA*008-HLA-B*13-Cw*0602 and MICA*010-HLA-B*4601-Cw*01 were significantly increased in both Types I and II, whereas MICA*002-HLA-B*38-Cw*07 (01-03) and MICA*017-HLA-B*57-Cw*0602 were elevated only in Type I. MICA*010 was in strong linkage with Cw*01. Analysis of independent association of MICA*010 in individuals lacking Cw*01 failed to maintain an association. Our results suggest that a significant increase of the MICA alleles in the patient group is a part of HLA-B-Cw haplotypes. It is conceivable that an unknown susceptibility gene, on certain HLA-B-Cw haplotypes, is responsible for the development of psoriasis.

Distributions of HLA-DRB1/DQB1 alleles and haplotypes in the north-eastern Thai population: indicative of a distinct Thai population with Chinese admixtures in the central Thais.

The phenotype and gene frequencies of HLA class II alleles were studied in the North-eastern Thai population. Blood samples were collected from 100 unrelated healthy North-eastern Thais. The HLA-DRB1 and DQB1 genes were typed using the polymerase chain reaction--sequence specific primer (PCR-SSP) and polymerase chain reaction--sequence specific oligonucleotide probe (PCR-SSO) techniques. Twenty-six HLA-DRB1 and 11 DQB1 alleles were found in this population. DRB1*1202, 1502, 0405 and DQB1*0502/0504, 0301/0304 alleles were commonly found. Linkage disequilibrium analysis suggested the existence of 13 DR-DQ haplotypes. The DRB1*1502-DQB1*0501 haplotype was the most common. The DRB1*1106-DQB1*0301/0304 haplotype was found only in North-eastern Thais and not in other Thai populations. Comparative analysis of the HLA-DR/DQ alleles revealed differences in the distributions of these alleles amongst different ethnic groups. Interestingly, the distributions of HLA class II alleles in Central Thai, North-eastern Thai and Southern Chinese populations are similar. However, it appears that the distribution in the Central Thais is a mixture of those in Southern Chinese and North-eastern Thais, suggesting the existence of Thai-Chinese admixtures in the Central Thai population. This study provides basic information for further studies of the MHC in anthropology, organ transplantation and disease susceptibility in the North-eastern Thai population.

Diversity of MICA (PERB11.1) and HLA haplotypes in Northeastern Thais.

MICA or PERB11.1 is a polymorphic major histocompatibility complex (MHC) class I-related gene located 46 kb centromeric of the HLA-B gene in the HLA class I region. It is expressed mainly in gut epithelial cells, keratinocytes, endothelial cells, fibroblasts and monocytes, and is upregulated by heat stress. MICA has been found to interact with gamma delta T cells, alpha beta CD8(+) and natural killer (NK) cells bearing the NKG2D/DAP10 receptor. The MICA gene displays a high degree of polymorphism with at least 54 alleles. In the present study, polymorphic exons 2, 3 and 4 of the MICA gene were analyzed using sequencing based typing (SBT) in 255 unrelated healthy northeastern Thais. Thirteen previously reported MICA alleles were detected. MICA*008, *010, *002 and *019 were highly predominant with the allele frequencies of 21.4%, 18.2%, 17.6% and 15.3%, respectively. Five of these 13 MICA alleles show significantly different frequencies from those of the Japanese and Caucasian populations. Interestingly, MICA052, which is a very rare allele in other populations, was prevalent with the allele frequency of 8.2%, mainly on the HLA haplotype carrying HLA-B*13 in this population. Strong linkage disequilibria were observed between MICA and HLA-B, as similarly observed in other populations, namely MICA*010-B*4601, MICA052-B*13, MICA*002-B*5801, and MICA*019-B*15 (1502, 1508, 1511, 1515, 1528, 1530). A large variety of three-locus (MICA - HLA-B - HLA-Cw) and six-locus (HLA-DQB1 - HLA-DRB1 - MICA - HLA-B - HLA-Cw - HLA-A) haplotypes were recognized in the northeastern Thai population. This is the first report on MICA allelic distribution in Southeast Asian populations. These data will provide the important basis for future analyses on the potential role of the MICA gene in disease susceptibility and transplantation matching in Southeast Asian populations.

Corneodesmosin gene: no evidence for PSORS 1 gene in North-eastern Thai psoriasis patients.

Psoriasis vulgaris, a common inflammatory skin disorder, is known to be associated with the HLA-Cw*06 allele. It has been recently suggested by microsatellite mapping that a real susceptible gene for psoriasis resides in the approximately 100-kb genomic region telomeric of the HLA-C gene. In this respect, the corneodesmosin (CDSN) gene 160-kb telomeric of HLA-C is a strong candidate because of its location and its functional role in corneocyte cohesion and desquamation. In fact, a significant association between CDSN polymorphism and psoriasis was recently recognized in Caucasian populations. However, this association has not been replicated in other studies, being still controversial. In this study, we investigated the genetic polymorphism of the CDSN gene in 139 psoriasis patients and 144 healthy controls in the North-eastern Thai population. By direct sequencing technique, a total of 28 polymorphic sites were found, consisting of 26 single nucleotide polymorphisms (SNPs) and two indels (insertion/deletion). Among them, six SNPs have not been previously reported. Through this analysis, as many as 28 different SNP/indel haplotypes within the CDSN gene were identified. Seven SNPs and one indel, namely 9C, 614 A, 722T, 971T, 1215G, 1243C, 1331G and 1606AAG (deletion), revealed significant deviation in the allelic frequencies of the patients from those of the healthy controls. However, none of them are likely to be responsible for controlling the susceptibility of psoriasis, but these associations can be explained by a linkage disequilibrium to a real pathogenic allele of a nearby gene. Further, the large variations between the CDSN SNP/indel haplotypes and the psoriatic major histocompatibility complex (MHC) haplotypes also make it unlikely that CDSN is a major psoriasis-susceptible gene.