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.

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.

Reducing the risk of HIV transmission through blood transfusion by donor self-deferral.

A cross sectional study was conducted to evaluate the validity of implementing a blood donor self-deferral form for reducing the risk of HIV transmission through blood transfusion. The self-deferral form which was given to all blood donors, included questions about HIV risk factors in the three month period prior to blood donation. Donors were asked to declare confidentially whether their blood was safe for transfusion or not. Blood was collected and examined for HIV antigen, anti-HIV antibodies, HBsAg and syphilis antibodies. All of the serological markers detected among high risk donors and general donors were compared and analysed by Yates corrected X2 test and one-tailed Fisher's exact test with a significance level of 0.05. There were 401 self-deferred high risk donors and 15,523 general donors. The HIV antigen was found as a single marker in only one male high risk individual. The prevalence of anti-HIV antibodies, HBsAg and syphilis antibodies among the general donors was 0.61%, 5.29% and 1.17%, respectively. The anti-HIV, HBsAg and syphilis antibodies in the high risk donors were 1.99%, 7.98% and 1.25%, respectively. In comparison with the general donors, the high risk donors demonstrated statistically significant higher prevalence rates of HIV antigen (p < 0.05), anti-HIV (p < 0.005) and HBsAg (p < 0.05). In conclusion, donor self-deferral is valid for reducing the risk of HIV transmission through blood transfusion and its implementation should be encouraged when recruiting blood donors.

Anti-HIV antibody titer: an alternative supplementary test for diagnosis of HIV-1 infection.

The diagnosis of HIV infection is based on screening of HIV antibodies and confirmed by a more specific supplementary test. The most common confirmation test is Western blot, which is expensive, time consuming and subject to technical skill. The present study was carried out to evaluate whether the anti-HIV-1 antibody titer is valid as a supplementary test for diagnosis of HIV-1 infection. Anti-HIV-1 antibody titers of 2,414 anti-HIV-1 positive sera determined by the particle agglutination (PA) method were analysed in comparison with the Western blot analysis. The Western blot negative result was found in 11 of 2,414 (0.46%) anti-HIV-1 positive sera, these sera also gave negative anti-HIV by ELISA. The PA titers of these sera were found in the range of 16 to 64. Seventeen samples (0.70%) with anti-HIV-1 in the titer range of 16 to 256 showed indeterminate Western blot analysis. The rest, 2,386 of these 2,414 sera (98.84%), were shown to be positive by Western blot. However, all of the 2,356 sera with antibody titers > or = 512 (97.6%) demonstrated positive Western blot results. Five cases among the 17 (29.4%) indeterminate sera were examples of early seroconversion of HIV infection, which were confirmed in follow up specimens. The results suggest that only the samples with antibody titers < 512 are required to be confirmed for HIV infection by Western blot. It is possible that early seroconversion may be inferred from anti-HIV titers. Therefore, in order to reduce time and cost, the PA anti-HIV titer can be used as an alternative supplementary test for diagnosis of HIV-1 infection in most positive screened anti-HIV samples. Western blot is needed for testing in only a few cases.

Preliminary survey of anti-HTLV-I in northeastern-Thais.

The anti-HTLV-I prevalence was studied by particle agglutination technique (PA) in 2,609 samples including: 403 antenatal care women from Srinagarind Hospital, Faculty of Medicine, 342 high-risk sexually transmitted disease blood donors and 1,864 randomly selected blood donors from the Blood Transfusion Centre, Faculty of Medicine, Khon Kaen University. All of the 2,609 samples gave negative anti-HTLV-I. The result revealed that HTLV-I infection is not common in northeast-Thailand. However, as the sample size from this study may be too small, further study should be carried out.

Seroepidemiology of HTLV-I infection in northeast Thailand: a four year surveillance.

The human T-lymphotropic virus type I (HTLV-I) can be transmitted through blood transfusion, sexual contact, perinataly and by breast feeding. We carried out a four years seroepidemiology surveillance study of HTLV-I infection among northeast Thai population by screening for antibodies to HTLV-I (anti-HTLV-I) in 1992, 1993, 1995 and 1997. A total of 8,323 blood samples were collected from 6,228 blood donors, 832 pregnancies, 219 multitransfused patients, 53 HIV positive intravenous drug users and 1,000 northeast-Thai workers at different periods of time. The serum samples were tested for anti-HTLV-I by particle agglutination (PA) technique and confirmed by Western blot. One sample from a multitransfused patient collected in 1992 and one sample from a blood donor collected in 1995 demonstrated positive anti-HTLV-I screening by PA but negative by Western blot. This finding indicates that at present HTLV-I is not a public health problem in the northeast of Thailand but surveillance should be continually conducted.

Association of HCV and Treponema pallidum infection in HIV infected northeastern Thai male blood donors.

The study was performed to determine the association of seroprevalence of hepatitis C virus (HCV) and Treponema pallidum (T. pallidum) infection among HIV infected first time male blood donors (HIV group) in comparison with the HIV seronegative blood donors (control group) in the Northeast of Thailand (NET). Serum samples were collected from 10,321 first blood donation voluntary male donors. All samples were screened for anti-HIV and anti-HCV by particle agglutination test, and syphilis antibody by RPR. The anti-HIV positive sera were repeated by EIA and confirmed by western blot. The reactive anti-HCV samples were confirmed by EIA whereas reactive syphilis antibody samples were confirmed by TPPA. Fisher's exact test was used for statistical analysis. The prevalence of anti-HIV in first time male donors was 0.70 per cent (72/10,321). The age of HIV group and 10,018 male control group ranged from 17-50 years old. The prevalence of HIV among 21-40 years old age group was significantly higher than the 17-20 years old (p = 0.00003). The 17-20 years old HIV group showed significantly higher sero-prevalence of TPPA (p = 0.003). The 21-30 years old HIV group gave significantly higher sero-prevalence of anti-HCV (p = 0.0008) and TPPA (p = 0.045), but the seroprevalence of anti-HCV and TPPA among the 31-50 year old group were nonsignificantly different (p > 0.05). The concurrence of anti-HCV and TPPA in HIV groups was not found. This result indicated that HIV infection among NET voluntary male blood donors was significantly associated with T. pallidum infection in young adults and the HCV infection in mature adults.

PIP: This study was performed to determine the association of seroprevalence of hepatitis C virus (HCV) and Treponema pallidum infection among HIV-infected first-time male blood donors (HIV group) in comparison with HIV-seronegative blood donors (control group) in northeastern Thailand (NET). Serum samples were collected from 10,321 first-time voluntary male blood donors. All samples were screened for anti-HIV and anti-HCV by particle agglutination test and for syphilis antibody by RPR. The anti-HIV-positive sera were submitted to EIA and confirmed by Western blot. The reactive anti-HCV samples were confirmed by EIA, whereas reactive syphilis antibody samples were confirmed by T. pallidum particle agglutination (TPPA) test. Fisher's exact test was used for statistical analysis. The prevalence of anti-HIV in first-time male donors was 0.70% (72/10,321). The age range of HIV group and control group donors was 17-50 years. The prevalence of HIV infection among the 21-40 age group was significantly higher than among the 17-20 age group (p = 0.00003). The 17-20 year old HIV group donors showed significantly higher seroprevalence of TPPA (p = 0.003). The 21-30 year old HIV group donors had significantly higher seroprevalence of anti-HCV (p = 0.0008) and TPPA (p = 0.045), but the seroprevalences of anti-HCV and TPPA among the 31-50 age group were nonsignificantly different (p 0.05). Concurrence of anti-HCV and TPPA in HIV groups was not found. This result indicates that HIV infection among NET voluntary male blood donors was significantly associated with T. pallidum infection in young adults and with HCV infection in mature adults.

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.

Distribution of HLA-A and B antigens in northeastern-Thais.

The phenotype and gene frequencies of HLA class I were studied in the Northeastern Thai population. Blood samples were collected from 100 unrelated healthy Northeastern Thais. HLA-A and B antigens were typed by using the standard microlymphocytotoxicity test. Twelve HLA-A and twenty-five HLA-B antigens were found in this population. HLA-A2, A24, A11 and the HLA-B46, B15, B22 antigens are commonly found in this group. Linkage disequilibrium analysis indicated the existence of fifteen haplotypes. The HLA-A2, B46 haplotype was the most common. These results will be useful for further studies in anthropology, organ transplantation and MHC associated disease in Northeastern Thais.

DNA typing of the HLA-A, -B and -C genes: possible MHC class I haplotypes in the northeastern-Thais.

The phenotype and gene frequencies of HLA class I were studied in the Northeastern Thai population. Blood samples were collected from 100 unrelated healthy northeastern-Thais. HLA-A, -B and -Cw alleles were determined using the polymerase chain reaction- amplification refractory mutation system (PCR-ARMS). 12 HLA-A, 20 HLA-B and 14 HLA-Cw alleles were found. Linkage disequilibrium analysis indicated the existence of 7 HLA-A-B and 19 HLA-B-Cw haplotypes. A*0207-Cw*01-B*4601 was the most common possible haplotype in this population. These results provide regional basic information for further studies in anthropology, organ transplantation and MHC disease associations in the northeastern-Thais.

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.

Frequency of human platelet antigens among blood donors in northeastern Thailand.

BACKGROUND: Platelet transfusions have been widely used in Thailand, but little is known about the phenotyping of human platelet antigens. STUDY DESIGN AND METHODS: Whole blood was collected from 483 blood donors for preparation of platelets. An improved mixed passive hemagglutination assay was used for this study. RESULTS: Frequencies demonstrated were 100 percent for HPA-1a (PlA1), 15.94 percent for HPA-2b (Siba), 60.25 percent for HPA-3a (Baka), 98.76 percent for HPA-4a (Yukb), 1.86 percent for HPA-4b (Yuka), 5.38 percent for HPA-5b (Br(a)), and 97.72 percent for Naka. CONCLUSION: HPA-1a was found in 100 percent of Thais, which is the same frequency as in other Asian populations but somewhat different from that in whites (97.9%). Therefore, HPA-1a will not cause neonatal alloimmune thrombocytopenia or post-transfusion purpura in Thais. According to the frequencies of HPA-2b, HPA-3a, HPA-4a, HPA-4b, HPA-5b, and Naka antigens, they may induce neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet refractoriness in Thais.

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.