HLA-DQA1*04: 01 is related to a higher multiple sclerosis lesion load on T2/Flair MRI sequences / O HLA-DQA1*04: 01 está relacionado com uma alta carga lesional na ressonância magnética em T2/Flair nos pacientes com esclerose múltipla

ABSTRACT Background: The genetic predisposition to multiple sclerosis (MS) is associated with HLA alleles, especially HLA-DRB1*15:01. Objective: To identify associations between findings in magnetic resonance imaging (MRI) and genetic features in a Brazilian cohort of patients with MS. Methods: We retrospectively studied data from 95 consecutive patients with MS. Two independent observers who were blinded to the clinical data identified black holes and enhanced lesions on T1 MRI sequences, and counted and measured contrast-enhanced lesions on T2 and Flair (fluid attenuation inversion recovery) sequences. Cases were classified according to lesion size, number, and volume. The HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the rs4774, rs3087456, rs6897932, rs731236, and rs1033182 single nucleotide polymorphisms were identified by polymerase chain reaction amplification with sequence-specific primers using the One Lambda Inc. Kit, Canoga Park, CA, USA. Results: Patients with the HLA-DQA1*04:01 allele had lesion load (adjusted for age, sex, and MS duration) above median compared with patients with other HLA-DQA1 alleles (p=0.02). There were no differences among all the other HLA alleles and single nucleotide polymorphisms and lesion load. Conclusions: The correlation of the HLA-DQA1*04:01 allele with a higher lesion load on T2/Flair MRI sequences suggests that the presence of this allele is associated with the risk of greater MS severity.

RESUMO Antecedentes: A predisposição genética para a esclerose múltipla (EM) está associada a alelos HLA, principalmente o HLA-DRB1*15:01. Objetivo: Identificar associações entre lesões na ressonância magnética e características genéticas em uma coorte brasileira de pacientes com EM. Métodos: Estudamos retrospectivamente os dados de 95 pacientes consecutivos com EM. Dois observadores independentes que desconheciam os dados clínicos identificaram "black holes" e lesões realçadas pelo contraste nas sequências de ressonância magnética T1 e contaram e mediram as lesões nas sequências T2 e FLAIR (fluid attenuated inversion recovery). Os casos foram classificados de acordo com tamanho, número e volume da lesão. Os alelos HLA-DRB1, HLA-DQB1 e HLA-DQA1 e os polimorfismos de nucleotídeo único rs4774, rs3087456, rs6897932, rs731236 e rs1033182 foram identificados por amplificação de reação em cadeia da polimerase com iniciadores específicos de sequência usando o kit One Lambda Inc., Canoga Park, CA, EUA. Resultados: Os pacientes com alelo HLA-DQA1*04:01 apresentaram carga de lesão (ajustada para idade, sexo e duração da EM) acima da mediana em comparação com outros pacientes com demais alelos HLA-DQA1 (p=0,02). Não houve diferenças entre todos os outros alelos HLA e polimorfismos de nucleotídeo único e carga lesional. Conclusões: A correlação do alelo HLA-DQA1*04:01 com maior carga de lesão nas sequências de RM em T2 sugere que a presença desse alelo pode estar associada ao risco de maior gravidade da EM.

Search for DQ2 5 and DQ8 alleles using a lower cost technique in patients with type 1 diabetes and celiac disease in a population of southern Brazil

ABSTRACT Objective To evaluate the frequency of DQ2.5 and DQ8 alleles using the Tag-single-nucleotide polymorphism (Tag-SNP) technique in individuals with type 1 diabetes mellitus (T1DM) and celiac disease (CD) in southern Brazil. Materials and methods In a prospective design, we performed the search for DQA1*0501 and DQB1*0201 alleles for DQ2.5 and DQB1*0302 for DQ8 through Real-Time Polymerase Chain Reaction (RT-PCR) technique, using TaqMan Genotyping Assays (Applied Biosystems, USA). The diagnosis of CD was established by duodenal biopsy and genotypic determination performed by StepOne Software v2.3. Allelic and genotypic frequencies were compared between groups using Chi-square and Fisher's exact tests and the multiple comparisons using Finner's adjustment. Results Three hundred and sixty two patients with a median age of 14 years were divided into 3 groups: T1DM without CD (264); T1DM with CD (32) and CD without T1DM (66). In 97% of individuals with T1DM and CD and 76% of individuals with CD without T1DM, respectively, the alleles DQ2.5 and/or DQ8 were identified (p < 0.001). DQ2.5 was more common in individuals with CD (p = 0.004) and DQ8 was more common in individuals with type 1 diabetes (p = 0.008). Conclusions The evaluation of the alleles for DQ2.5 and DQ8 by Tag-SNP technique showed a high negative predictive value among those with T1DM, similar to that described by the conventional technique. The high frequency of DQ8 alleles in individuals with T1DM did not allow differentiating those at higher risk of developing T1DM.

Papilomatosis respiratoria recurrente en paciente pediátrico: reporte de un caso / Recurrent respiratory papillomatosis in a pediatric patient: case report

La variabilidad genética relacionada al sistema inmune del huésped ha sido propuesta como uno de los factores más influyentes en el desarrollo de enfermedades causadas por HPV. Caso clínico: Reportamos el caso de un niño de 5 años en cuyo estudio por disfonía crónica se encuentra papilomatosis laríngea probablemente adquirida por vía vertical durante el parto. El diagnóstico de papilomatosis laríngea se confirmó con una biopsia tras una primera cirugía orientada a remover los papilomas. Se utilizó el sistema de clasificación Derkay para evaluar la severidad de la papilomatosis. Se realizó genotipificación en biopsia demostrándose HPV-6. Posteriormente mediante tipificación de alelos HLA se demostró homocigosis para los alelos HLA-DQA1*0505, -DQB1*0301, -DRB1*1101. Conclusiones: Se necesitan estudios adicionales que permitan identificar los alelos HLA más prevalentes en población latina y su potencial asociación con la susceptibilidad genética en Papilomatosis Respiratoria Recurrente.

Genetic variability related to the host immune system has been proposed as one of the most influential factors in the development of diseases caused by HPV. Clinical case: We report the case of a 5-year-old child in whom chronic laryngeal papillomatosis, probably acquired vertically during labor, was detected. The diagnosis of laryngeal papillomatosis was confirmed with a biopsy after a first surgery to remove the papillomas. The Derkay classification system was used to assess the severity of papillomatosis. Biopsy genotyping was performed by demonstrating HPV-6. Later, HLA-DQA1 * 0505, -DQB1 * 0301, -DRB1 * 1101 alleles were homozygous for HLA allele typing. Conclusions: Further studies are needed to identify the most prevalent HLA alleles in the Latino population and their potential association with genetic susceptibility in Recurrent Respiratory Papillomatosis.

Study of polymorphisms of HLA class Ⅰ (-A, -B, -C) and class Ⅱ (DRB1, DQA1, DQB1, DPA1, DPB1) genes among ethnic Hans from Southern China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the genetic polymorphisms of human leukocyte antigen (HLA)- A, B, C, DRB1, DQA1, DQB1, DPA1and DPB1among ethnic Hans from southern China.</p><p><b>METHODS</b>481 randomly selected individuals were genotyped using a polymerase chain reaction (PCR) sequence-based typing (SBT) method for the above genes. Their allele frequencies were determined by direct counting.</p><p><b>RESULTS</b>In total, 28 HLA-A, 57 HLA-B, 28 HLA-C, 40 HLA-DRB1, 18 HLA-DQA1, 17 HLA-DQB1, 6 HLA-DPA1and 21 HLA-DPB1alleles were identified. Among these, common alleles (with allelic frequencies > 0.05) included A*1101, A*2402, A*0207, A*3303, A*0201, B*40:01, B*46:01, B*58:01, B*13:01, B*15:02, C*01:02, C*07:02, C*03:04, C*03:02, C*08:01, C*03:03, C*04:01, DRB1*09:01, DRB1*15:01, DRB1*12:02, DRB1*08:03, DRB1*03:01, DRB1*04:05, DRB1*11:01, DQA1*01:02, DQA1*03:02, DQA1*03:03, DQA1*06:01, DQA1*01:03, DQA1*05:05, DQA1*01:04, DQA1*03:01, DQA1*05:01, DQB1*03:01, DQB1*03:03, DQB1*06:01, DQB1*05:02, DQB1*03:02, DQB1*02:01, DQB1*03:02, DQB1*06:02, DPA1*02:02, DPA1*01:03, DPA1*02:01, DPB1*05:01, DPB1*02:01, DPB1*13:01, DPB1*04:01and DPB1*02:02.For each of the locus, the overall frequencies of common alleles were 75.57%, 52.81%, 78.28%, 62.16%, 86.70%, 77.23%, 95.32% and 81.59%, respectively.</p><p><b>CONCLUSION</b>The allelic frequencies of the 8 selected HLA loci among ethnic Hans from southern China may served as a reference for anthropology, legal medicine, transplantation and disease association studies.</p>

Analysis of the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion among ethnic Han Chinese from Wenzhou region / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) among ethnic Han Chinese from Wenzhou region.</p><p><b>METHODS</b>Fifty couples with URSA (URSA group) and 66 couples with normal pregnancy history (control group) were recruited. The alleles of HLA-DQA1 and HLA-DQB1 were analyzed by polymerase chain reaction with specific sequence primers (PCR-SSP) in all subjects. The frequency distribution of HLA-DQ alleles, odds ratios (OR) between each group and sharing of HLA-DQ alleles were calculated.</p><p><b>RESULTS</b>The frequency distribution of HLA-DQB1*03:03 allele in the females with URSA was significantly higher than that healthy females (21.00% vs. 9.85%, OR=2.433, 95%CI: 1.232-4.894, χ(2)=5.657, P<0.05). The HLA-DQB1*05:03 allele was present among the healthy females with a frequency of 3.03%, and was not detected among females with URSA. For both males and females, the HLA-DQB1*05:02 allele were only typed in control group with frequencies of 6.06% and 5.30%, respectively. The sharing of HLA-DQA1 alleles in couples with URSA was increased compared with the control group (70.27% vs. 44.64%, OR=2.931, 95%CI: 1.216-7.067, P<0.05).</p><p><b>CONCLUSION</b>The increased sharing of HLA-DQA1 alleles may contribute to the susceptibility of URSA among ethnic Han Chinese from Wenzhou region. The allele of HLA-DQB1*03:03 in the females may be predisposing factor for URSA. However, the HLA-DQB1*05:02 allele in both gender and HLA-DQB1*05:03 allele in females may confer a protective effect.</p>

Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy.</p><p><b>METHODS</b>Totally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared.</p><p><b>RESULTS</b>Different treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both).</p><p><b>CONCLUSIONS</b>Both constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.</p>

Association of HLA-DQA1 gene rs9272346 polymorphism with clinical outcome of hepatitis B virus infection in ethnic Han population from Hubei / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of rs9272346 polymorphism of HLA-DQA1 gene with clinical outcome of hepatitis B virus (HBV) infection in ethnic Han population from Hubei, China.</p><p><b>METHODS</b>A case-control study was conducted, which have involved 1028 unrelated subjects including 238 asymptomatic HBV carriers (AHC), 173 acute liver failure (ALF), 292 liver cirrhosis (LC) and 325 hepatocellular carcinoma (HCC). Genotypes of rs9272346 were determined by real-time polymerase chain reaction with a TaqMan MGB probe. Statistical results were analyzed using Chi square test, student's t test and unconditional logistic regression.</p><p><b>RESULTS</b>No significant differences were detected in the frequencies of G allele between ALF, LC, HCC and AHC groups (P= 0.312, 0.314, 0.264). Compared with the AA genotype, the GG and GA genotypes were not associated with the patients groups under the dominant model: ALF group vs. AHC group (adjusted OR= 1.08, 95%CI: 0.7-1.68), LC group vs. AHC group (adjusted OR= 1.11, 95%CI: 0.87-1.26), HCC group vs. AHC group (adjusted OR= 0.93, 95%CI: 0.65-1.33). For women, the GG and GA genotypes have conferred a protective effect for the outcome of ALF (OR= 0.30, 95%CI: 0.1-1.87).</p><p><b>CONCLUSION</b>Our results suggested that rs9272346 polymorphism of HLA-DQA1 may not independently influence the outcome of HBV infection in ethnic Han Chinese in Hubei, while the GG and GA genotypes may confer a protective effect against ALF in women.</p>

Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and anti-angiogenic activities in gender-specific gene expression in Keshan disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Keshan disease (KD) is an endemic cardiomyopathy in China. The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease. Young women of child-bearing age are the most frequent victims in rural areas. The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers.</p><p><b>METHODS</b>We extracted RNA from the peripheral blood mononuclear cells of KD patients (12 women and 4 men) and controls (12 women and 4 men). Then the isolated RNA was amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Gene expression was examined using oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was also performed to validate our microarray results.</p><p><b>RESULTS</b>Among the genes differentially expressed in female KD patients we identified: HLA-DOA, HLA-DRA, and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7, involved in cardiomyocyte differentiation defect; and ADAMTS 8, CCL23, and TNFSF15, implicated in anti-angiogenic activities. These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD.</p><p><b>CONCLUSION</b>Our results might help to explain the higher susceptibility of women to this disease.</p>

Study on the correlation between chronic asymptomatic HBV carriers of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study on the correlation between chronic asymptomatic HBV carriers (ASC) of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles.</p><p><b>METHODS</b>Totally 105 ASC were assigned to two groups according to their constitutions, i.e., the yin asthenia group (47 cases) and the non-yin asthenia group (58 cases). The genotypes of HLA-DRB1 and HLA DQA1 alleles were determined using PCR-SSP.</p><p><b>RESULTS</b>The gene frequency of HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele (being 12.1% and 19.1%) were obviously lower in the yin asthenia group than in the non-yin asthenia group (being 27.8% and 39.7%, P < 0.05). The gene frequency of HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele were obviously higher in the yin asthenia group (being 12.1% and 28.7%) than in the non-yin asthenia group (4.3% and 9.5%), showing statistical difference (P < 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele might be the molecular bases for non-yin asthenia patients with ASC. HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele might be the molecular bases for yin asthenia patients with ASC.</p>

Association between HLA-DQA1 gene copy number polymorphisms and susceptibility to gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the association between HLA-DQA1 gene copy number polymorphisms and gastric cancer risk in Chinese population, and the interaction of those genes and environmental factors.</p><p><b>METHODS</b>The genotype of HLA-DQA1 gene copy number polymorphisms was determined in 343 patients with gastric cancer and 330 controls by quantitative polymerase chain reaction. Logistic regression model was used to evaluate the impact of this polymorphism on the risk of developing gastric cancer and the gene-environment interaction.</p><p><b>RESULTS</b>Compared with 0 copy of HLA-DQA1 gene carriers, the 2 copies of HLA-DQA1 gene carriers had a significantly increased risk of gastric cancer (OR = 1.87, 95%CI = 1.15 - 3.06, P = 0.012). Gene-environment interaction of HLA-DQA1 gene copy number polymorphisms and Helicobacter pylori infection significantly increased the risk of gastric cancer in a multiplicative manner, with an OR of 3.89 (95%CI = 1.75 - 8.57, P = 0.001).</p><p><b>CONCLUSIONS</b>HLA-DQA1 gene copy number polymorphism is associated with gastric cancer susceptibility, and there is a multiplicative gene-environment interaction between this polymorphism and Hp infection in the development of gastric cancer.</p>

Study of the correlation between 51 immune infertility patients of the Han nationality in Anhui and HLA-DQA1 gene and treatment of Mianbu III / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the correlation between anti-sperm antibody-positive immune infertility patients and human leucocyte antigen (HLA) DQA1 gene, and to study the correlation between the treatment of Chinese medicine and pharmacy and HLA-DQA1 genotype.</p><p><b>METHODS</b>The polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used in studying HLA-DQA1 genotypes of 51 anti-sperm antibody-positive immune infertility patients and 60 healthy subjects. Mianbu III (consisting of rehmannia root, white peony root, Fructus Comi, yam, barbary wolfberry fruit, moutan bark, and dwarf lilyturf root) was used in patients for three months.</p><p><b>RESULTS</b>The HLA-DQA1 *0401 allele in the immune infertility group was obviously higher than that in the healthy control group (chi2 = 29.869, P < 0.01). As for the therapeutic efficacy 22 cases of the 27 positive HLA-DQA1 * 0401 turned to negative with statistical difference (chi2 = 5.24, P = 0.022).</p><p><b>CONCLUSION</b>HLA-DQA1 *0401 allele might be predisposing gene of the anti-sperm antibody-positive immune infertility. The Chinese medicinal treatment was effective for the HLA-DQA1 *0401 allele patients.</p>

Association of chinese medicine constitution and human leukocyte antigen-DQA1 gene polymorphism with outcomes of hepatitis B virus infection / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the Chinese medicine constitution types and human leukocyte antigen (HLA)-DQA1 gene polymorphism in patients with hepatitis B (HB) virus infection in Chinese Han population of Zhejiang Province, for exploring the roles of constitution factor in pathogenesis of HB.</p><p><b>METHODS</b>A total of 240 subjects, including 120 biopsy-proven chronic HB (CHB), 60 HB asymptomatic carrier (ASC) and 60 resolved from HBV infection spontaneously (RHBS) were studied. Their Chinese medicine constitution type was judged by Wangqi's classification, and their genotype of HLA-DQA1 was detected by polymerase chain reaction sequence specific primer for comparing the difference between groups in distribution frequency (DF) of constitution types and genes.</p><p><b>RESULTS</b>(1) As compared with the RHBS group, DF of yin-deficiency constitution and phlegm-dampness constitution in the CHB group was significant higher (20.0% vs. 6.7% and 12.5% vs. 1.7%), and that of placid constitution was significant lower (11.7% vs. 31.7%), showing statistical significance between groups (OR = 3.5, 95% CI: 1.16-10.60; OR = 8.4, 95% CI: 1.09-65.42; OR = 0.161, 95% CI: 0.076-0.34; all P < 0.05). (2) As compared with the ASC group, DF of damp-heat constitution was significant higher (24.2% vs. 6.7%, P < 0.05, OR = 4.462, 95% CI: 1.49-13.36), and that of placid constitution was significant lower (11.7% vs. 45.0%, P < 0.01, OR = 0.285, 95% CI: 0.13-0.62) in the CHB group. (3) As compared with RHBS group, DF of HLA-DQA1 * 0201 allele in CHB group was significant higher (38.3% vs. 5.8%, P < 0.01, OR = 10.04, 95% CI: 4.48-22.48); and that of HLA-DQA1 * 0102 allele was significant lower (9.6% vs. 36.7%, P < 0.01, OR = 0.183, 95% CI: 0.10-0.32). (4) As compared with ASC group, DF of HLA-DQA1 * 0201 allele in CHB group was significant higher (38.3% vs. 7.5%, P < 0.01, OR = 7.667, 95% CI: 3.7-15.87), and that of HLA-DQA1 * 0102 allele was significant lower (20.0% vs. 9.6%, P < 0.01, OR = 0.424, 95% CI: 0.23-0.79).</p><p><b>CONCLUSION</b>Both Chinese medicine constitution and HLA-DQA1 gene polymorphism show connection with the outcomes of HB virus infection in Chinese Han population, but the real association between them is required for further study.</p>

Association between HLA-DQA1 gene polymorphism and the outcomes of hepatitis B virus infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the association between HLA-DQA1 gene polymorphism and the outcomes of hepatitis B virus infection in Chinese Han population.</p><p><b>METHODS</b>A total of 180 consecutive patients with biopsy-proven hepatitis B virus infection (120 patients with chronic hepatitis B and 60 patients with asymptomatic HBV carrier) and 60 subjects who resolved from HBV infection spontaneously were studied. Genotype of human leukocyte antigen(HLA)-DQA1 was detected by polymerase chain reaction sequence specific primer(PCR-SSP).</p><p><b>RESULTS</b>(1) The frequency of HLA-DQA1 * 0201 allele in chronic hepatitis B group was significant higher than the frequency in resolved from HBV infection spontaneously group (38.3% vs. 5.8%, P < 0.001, A = 10.04, 95% CI: 4.48-22.48). The frequency of HLA-DQA1 * 0102 allele in chronic hepatitis B group was significant lower than the frequency in resolved from HBV infection spontaneously group (9.6% vs. 36.7%, P < 0.001, A = 0.183, 95% CI: 0.10-0.32). (2) The frequency of HLA-DQA1 * 0201 allele in chronic hepatitis B group was significant higher than the frequency in asymptomatic HBV carrier group (38.3% vs. 7.5%, P < 0.01, A = 7.667, 95% CI:3.7-15.87). The frequency of HLA-DQA1 * 0102 allele in chronic hepatitis B group was significant lower than the frequency in asymptomatic HBV carrier group (20% vs. 9.6%, P < 0.01, A = 0.424, 95% CI: 0.23-0.79).</p><p><b>CONCLUSION</b>HLA-DQA1 gene polymorphism may play an important role in the outcomes of hepatitis B virus infection in-Chinese Han population. The HLA-DQA1 * 0102 allele could keep individuals away from HBV infection, and HLA-DQA1 * 0201 allele could aggravate persistant infection of HBV and hepatic inflammatory.</p>

Association of haplotype formed on HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of haplotype of HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection in Han population of north China.</p><p><b>METHODS</b>Two hundred and seven chronic hepatitis B (HB) patients, two hundred and twelve chronic asymptomatic hepatitis B virus (HBV) carriers (HBV carrier) and one hundred and forty-eight self-limited HBV infection were investigated for HLA-DRB1 and HLA-DQA1 alleles by sequence specific-polymerase chain reaction (PCR-SSP).</p><p><b>RESULTS</b>The frequency of DRB1*04-DQA1*0301 haplotype was 10.03% in self-limited HBV infection subjects, significantly higher than that in chronic HB patients (3.66%) (P=0.0005)ûthe frequency of DRB1*15/*16-DQA1*0102 haplotype was 6.80% in self-limited HBV infection subjects, significantly higher than 1.94% in chronic HB patients (P=0.0012) and 1.65% in asymptomatic HBV carriers (P=0.0004)ûwhile the frequency of DRB1*04-DQA1*0302 haplotype was 3.10% in chronic HB patients, higher than that in self-limited HBV infection subjects (0.39%) (P=0.0077).</p><p><b>CONCLUSION</b>Individuals with different haplotypes composed of HLA-DRB1 and HLA-DQA1 might have different outcomes of HBV infection.</p>

The genetic polymorphism of HLA-DQA1 and HLA-DQB1 genes of Chinese Han population in Jiangsu area is studied by PCR-sequence-based typing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the polymorphism of HLA-DQA1 and DQB1 genes of Han population in Jiangsu of China.</p><p><b>METHODS</b>The alleles and haplotypes frequencies of HLA-DQA1 and DQB1 genes in 100 unrelated healthy individuals were analyzed by using polymerase chain reaction-sequence-based typing (PCR-SBT).</p><p><b>RESULTS</b>Among the 7 DQA1 alleles detected, the most common allele was DQA1*0301/02/03 with a frequency of 29.5%, which was followed by DQA1*0501, DQA1*0102 and DQA1*0201 with frequencies of 18.5%, 17.0% and 12.5%, respectively. Of the 13 DQB1 alleles detected, DQB1*0201/02 allele (21.5%) was the most frequent allele, followed by DQB1*0301/09 (14.5%), DQB1*0303 (13.5%) and DQB1*0603 (11.5%). The most common DQA1 vs DQB1 haplotype was DQA1*0301/02/03 vs DQB1*0303 with a frequency of 12.5%, which was followed by the DQA1*0201-DQB1*0201/02 (10.5%),DQA1*0501-DQB1*0201/02 (9.5%) and DQA1*0501-DQB1*0301/09 (7.0%).</p><p><b>CONCLUSION</b>The distribution of HLA-DQ alleles and haplotypes in Jiangsu Han population shares some genetic characteristics with other population in northern of China, but has its own characteristics. The data will provide useful information for anthropology, organ transplantation and disease association studies.</p>

Association of polymorphisms of human leucocyte antigen -DRB1 and -DQA1 allele with outcomes of hepatitis B virus infection in Han population of north China / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess the association of polymorphisms of human leucocyte antigen (HLA) -DRB1 and -DQA1 region allele with outcomes of hepatitis B virus (HBV) infection in Han population of north China.</p><p><b>METHODS</b>A total of 207 chronic hepatitis B (HB) patients, 212 chronic asymptomatic HBV carriers (HBV carrier), and 148 self-limited HBV infection were recruited to examine the association between gene polymorphisms and outcomes of HBV infection. Polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to genotype HLA-DRB1 and HLA-DQA1 loci.</p><p><b>RESULTS</b>The frequency of HLA-DQA1 * 0301 in chronic HB patients (14.81%) was significantly lower than those in HBV carriers (25.24%) and self-limited HBV infection subjects (25.00%) (Pc = 0.002; Pc = 0.007). The frequency of HLA-DQA1 * 0102 in self-limited HBV infection subjects (8.78%) was significantly higher than those in chronic HB patients (2.18%) and HBV carriers (1.89%) (Pc = 0.000; P = 0.000). In addition, the frequency of HLA-DQA1 * 0302 in self-limited HBV infection subjects (4.05%) was significantly lower than that in chronic HB patients (11.41%) (Pc = 0.005). HLA-DQA1 * 0302 was demonstrated to be risk factors of chronic HBV (OR = 3.913, P = 0.0006), while HLA-DQA1* 0102 and HLA-DQA1 * 0301 to be protective factors against chronic HBV (OR = 0.200, P = 0.0004; OR = 0.258, P = 0.0000) after age, sex, smoking and drinking were adjusted by logistic regression analysis. There were positive interactions between drinking and HLA-DQA1 * 0102 [interaction index (II) = 1.49] or HLA-DQA1 * 0302 (II = 12.12). There were negative interactions between drinking and HLA-DQA1 * 0301 (II = 0.78)</p><p><b>CONCLUSIONS</b>The subjects with HLA-DQA1 * 0302 allele have an increased risk to chronic HB infection compared with other subjects without this allele, while HLA-DQA1 * 0301 and HLA-DQA1 * 0102 are associated with HBV clearness. Gene-environment interaction can affect the outcomes of HBV infection.</p>

HLA-DQA1 genotyping by using oligonucleotide microarrays / 中国实验血液学杂志

In order to fabricate the HLA-DQA1 genotyping chip and develop an integrated, parallel technical platform to type HLA system, a pair of primers and a set of probes were designed according to the sequences of HLA-DQA1 exon 2, where the polymorphism is concentrated. The oligonucleotide chip was made with the methods developed in our laboratory. The target DNA was asymmetrically amplified with the labeled sense primer. The signals were scanned and analyzed after the hybridization between microarray and PCR product. The allele types of the samples were identified. The result was verified by the standard DNA and DNA sequencing. The results showed that the genotyping was successfully carried out in 50 standard DNA samples and 50 clinical samples. Among them, results of the 50 standard DNA samples matched their templates. In the other 50 samples, results of the randomly selected 10 matched their sequencing results except that two of them got the incompletely result. In reproducible tests, the signal reappear rate was 95%. It is concluded that HLA-DQA1 genotyping by using our array system is simple and convenient with satisfied accuracy and reproducibility.

cDNA microarray and cluster analysis to identify the significance of immune genes associated with benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To delineate the immune regulatory pathway of benzene poisoning by using gene expression profile analysis.</p><p><b>METHODS</b>Peripheral white blood cell gene expression profile of 7 benzene poisoning patients, including one aplastic anemia, was determined by microarray. Seven chips from normal workers were served as controls. Cluster analysis of gene expression profile was performed. Differentially expressed immune genes associated with benzene poisoning were determined.</p><p><b>RESULTS</b>Among the 2 779 target genes, 38 genes differentially expressed were identified, including 10 up-regulated genes such as CD59, TRA@, MCP etc, and 14 down-regulated genes such as HLA-DMB, HLA-DQA1, HLA-DPB1, ITGB2, PFC etc. Cluster analysis showed that the expression profiles of 38 genes were associated with benzene poisoning.</p><p><b>CONCLUSION</b>Differentially expressed immune genes may play an important role in the pathogenesis of benzene poisoning.</p>

Association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes in Yi nationality of Yunnan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes in Yi nationality of Yunnan.</p><p><b>METHODS</b>Polymerase chain reaction with sequence-specific primers (PCR-SSP) genotyping method was conducted in 58 ethnic Yi patients with type 2 diabetes mellitus and 82 ethnically matched controls from Chuxiong of Yunnan. Then a study was made on the association between the polymorphism of HLA-DQA1 alleles and type 2 diabetes mellitus.</p><p><b>RESULTS</b>The frequency of HLA-DQA1*0301 allele in the patients with type 2 diabetes mellitus was significantly higher than that in the healthy controls (P=0.002, RR=3.097), and the frequency of HLA-DQA1*0601 in the patients was significantly lower (P=0.025, RR=0.429).</p><p><b>CONCLUSION</b>In Yi nationality of Yunnan, HLA-DQA1*0301 allele may be a susceptible gene and the HLA-DQA1*0601 allele may protect individuals from the risk of diabetes mellitus.</p>

Study on the polymorphisme of human leucocyte antigen-DRB1, -DQA1 and -DQB1 alleles in patients with hepatitis B / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the association between the polymorphism of human leucocyte antigen (HLA)-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B.</p><p><b>METHODS</b>HLA-DRB1, -DQA1 and -DQB1 alleles in 52 patients with chronic hepatitis B, 30 patients with acute hepatitis B and 106 normal control subjects were analysed, using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique.</p><p><b>RESULTS</b>The allele frequencies of HLA-DRB1 * 0301, -DQA1 * 0501 and -DQB1 * 0301 in the chronic hepatitis B group (17.31%, 25.96%, 35.58%) were markedly higher than that in the normal control group (5.67%, 13.36%, 18.87%), with statistical significance (chi(2)(1) = 12.3068, P(c1) = 0.0074; chi(2)(2) = 9.2002, P(c2) = 0.0157; chi(2)(3) = 15.5938, P(c3) = 0.0075). The allele frequencies of HLA-DRB1 * 1101/1104 and -DQA1 * 0301 in the chronic hepatitis B group (0.96%, 14.42%) were markedly lower than that in the acute hepatitis B group (13.33%, 30%), with significant correlation between them (chi(2)(1) = 11.9206, P(c1) = 0.0145; chi(2)(2) = 8.7396, P(c2) = 0.0167).</p><p><b>CONCLUSION</b>HLA-DRB1 * 0301, -DQA1 * 0501 and -DQB1 * 0301 were closely associated with the susceptibility to chronic hepatitis B, while HLA-DRB1 * 1101/1104 and -DQA1 * 0301 closely associated with the resistance to chronic hepatitis B. These findings suggested that host HLA class II gene was an important factor determining the outcome of HBV infection.</p>