Secondary type 1 narcolepsy after traumatic brain injury: a case report / 中华神经科杂志

Type 1 narcolepsy is a rare central nervous system disorder that is believed to result from the interaction of environmental and genetic factors. Traumatic brain injury (TBI) is one of the most common causes of secondary narcolepsy. Currently, there are very few reports on post-TBI narcolepsy, and this patient is the first reported case of HLA-DQB1 *06:02-positive type 1 narcolepsy following TBI in China. The clinical data of this patient are retrospectively analyzed to improve the understanding of the diagnosis and pathogenesis of the disease among clinicians.

Correlation between HLA-DQB1 and HLA-DRB1 gene polymorphisms and caries: a systematic review and Meta-analysis / 口腔疾病防治

Objective@#Systematic evaluation of the correlation of HLA-DQB1 and HLA-DRB1 allele polymorphisms with caries, to provide reference for caries prevention and treatment. @*Methods@# Relevant literature published before December 2020 was searched in the Cochrane Library, PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang, VIP, and CBM databases. Meta-analysis was performed using the R4.0.2 software to test for heterogeneity and evaluate the publication bias.@*Results @# In total,10 case-control studies were included with 564 people in the case group and 676 people in the control group. The results of the Meta-analysis show that: ① HLA-DQB1*02 (OR=0.52, 95%CI=0.29-0.93, P < 0.05) and HLA-DRB1*09 (OR=0.34, 95%CI=0.21-0.58, P < 0.05) are protective factors of dental caries; ② HLA-DRB1*13 (OR=2.96, 95%CI=2.03-4.33, P < 0.05) and HLA-DRB1*14 (OR=1.95, 95%CI=1.26-3.02, P < 0.05) alleles are risk factors for the development of dental caries. The results of the subgroup analysis are: HLA-DRB1*07 is a caries susceptibility factor in the Chinese population (OR=0.48, 95% CI=0.24-0.97, P < 0.05), while it is not statistically significant in the Brazilian and Turkish populations; HLA-DRB1*11 is a caries protective factor in the saliva group (OR=2.26, 95% CI=1.46-3.52, P < 0.05). 3.52, P < 0.001), while it is a caries susceptibility factor in the blood group (OR=0.09, 95% CI=0.12-0.34, P < 0.001). @*Conclusion @#HLA-DRB1*13 and HLA-DRB1*14 alleles are caries susceptibility genes, and HLA-DQB1*02 and HLA-DRB1*09 have protective effects on the caries development. HLA-DRB1*07 is a caries susceptibility gene in the Chinese population; HLA-DRB1*11 is a caries protective gene in the saliva group. Due to the limited sample size and quality of the included studies, more high-quality studies will be included later for verification.

Asociación genética entre los Loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a padecer Lupus eritematoso sistemático / Genetic association between the Loci HLA-DRB1 and HLA-DQB1 with susceptibility to suffer from systemic lupus erythematosus

La investigación en Inmunogenética brinda información acerca de marcadores genéticos asociados con enfermedades autoinmunes, como el Lupus Eritematoso Sistémico (LES), se puede observar entonces ciertos factores de riesgo o protección hacia la enfermedad en una población determinada. OBJETIVO: Determinar la asociación genética entre los polimorfismos del Complejo Principal de Histocompatibilidad (CPH) representados por los loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a LES. METODOLOGÍA: Se trabajó con 85 pacientes lúpicos y 85 pacientes sin la enfermedad; se obtuvo DNA humano a partir de sangre periférica, se realizó un PCR-SSP de baja y alta resolución para tipificar molecularmente a los loci HLA-DRB1 y HLA-DQB1. Se determinó las frecuencias alélicas, las cuales fueron asociadas con ambas muestras mediante el uso del Odds Ratio, a un nivel de significancia del 5 %. RESULTADOS: Los resultados del PCR-SSP de baja resolución muestran que ningún alelo HLA tiene un rol predisponente, se observó que el alelo HLA-DRB1*04 presenta un rol protector OR=0,49 (p=0,03). Los resultados por PCR-SSP de alta resolución muestran que los alelos HLA-DRB1*03:01 (OR=18,3; p=0,007), DRB1*04:04 (OR=4,2; p=0,009), DRB1*09:01 (OR=18,3; p=0,007), HLA-QB1*03:03 (OR=18,8; p=0,006) y DQB1*02:01 (OR=21,2; p=0,003) son factores de riesgo. Se evidenció que los alelos HLA-DRB1*08:02 (OR=0,42; p=0,003) y HLA-DQB1*04:02 (OR=0,50; p=0,02) son de carácter protector. CONCLUSIONES: Los alelos que representan riesgo de padecer LES en la muestra estudiada son HLA-DRB1*03:01, 04:04, 09:01 y HLA-DQB1*03:03, 02:01. Los alelos que tiene un carácter protector a la enfermedad son HLA-DRB1*08:02 y HLA-DQB1*04:02.

Immunogenetics research provides information on genetic markers associated with autoimmune diseases such as systemic lupus erythematosus (SLE), you can then observe certain risk factors or protection to the disease in a given population. To determine the genetic association between polymorphisms of the Major istocompatibility Complex loci represented by the HLA-DRB1 and HLA-DQB1 with susceptibility to SLE. METHODOLOGY: We worked with 85 lupus patients and 85 patients without the disease; Human DNA was obtained from peripheral blood, PCR-SSP low and high resolution molecularly performed to establish the loci HLA-DRB1 and HLA-DQB1. Allele frequencies, which were associated with both samples using the Odds Ratio at a level of significance of 5% were determined. RESULTS: Results of PCR-SSP low-resolution HLA show that no predisposing allele plays a role, we observed that HLA-DRB1*04 allele has a protective role OR=0.49 (p=0.03). The PCR-SSP results of high resolution show that the HLA-DRB1*03:01 alleles (OR=18.3; p=0.007), DRB1*04:04 (OR=4.2; p=0.009), DRB1*09:01 (OR=18.3; p=0.007), HLA-QB1*03:03 (OR=18.8; p=0.006) and DQB1*02:01 (OR=21.2; p=0.003) are risk factors. We demonstrated that HLA-DRB1*08:02 alleles (OR=0.42; p=0.003) and HLA-QB1*04:02 (OR=0.50; p=0.02) are of a protective nature. CONCLUSIONS: The alleles representing LES risk in the study sample are HLA-DRB1*03:01, *04:04, *09:01 and HLA-DQB1*03:03, *02:01. The alleles having a protective character to the disease are HLADRB1* 08:02 and HLA-DQB1*04:02.

Relationship between HLA-DQB1 allele polymorphism with HPV16 infection and cervical cancer susceptibility in Guangxi Zhuang women / 中国免疫学杂志

Objective:To study the relationship of Guangxi Zhuang women being infected by HPV16 and suffering from cervical cancer with HLA-DQB1 allele polymorphism.Provide clues for seeking hereditary susceptibility gene or resistant gene of cervical cancer of Guangxi Zhuang women.Methods:Chose the cervical cancer diagnosed female patients and health women 171 cases respectively aged between 25 and 45 of Guangxi as subject investigated(people in the two groups were paired by age ±3 years).Took their samples to extract HPV DNA and human genome DNA.Then detected HLA-DQB1 alleles and HPV genetype applying PCR-SSP and molecular diversion hybrid technology.Finally the data were statistically analyzed.Results:(1)The total infection rate of HPV in 171 cases of cervical cancer patient was 91.22%,in which the high-risk virus accounted for 90.76%,HPV16 was the main pathogenic subtypes(43.58%).(2)The allele carrying rate of HLA-DQB1*04 in the cervical cancer group was higher than the health control group with statistically significant difference(P0.05).(3)The occurrence frequency of HLA-DQB1*04 alleles in HPV16 positive cervical cancer patients was significantly higher than HPV16 negative patients with statistically significant difference(P<0.05).Conclusion:HLA-DQB1*04 alleles are probably the susceptibility genes of cervical cancer of Guangxi Zhuang women;HLA-DQB1*06/09 alleles are probably the protective genes of cervical cancer of Guangxi zhuang women;HLA-DQB1*02/05/07/08 alleles seem irrelevant to hereditary susceptibility of cervical cancer of Guangxi Zhuang women.And Guangxi Zhuang women carried HLA-DQB1*04 alleles are more likely to infect HPV16 that increase the risk of cervical cancer.

Relationship between HLA-DQB1 allele as well as expression level of Th1/Th2 cytokines with familial clustering of hepatocellular carcinoma in Guangxi yao / 中国免疫学杂志

Objective:To elucidate the relationship between HLA-DQB1 allele polymorphism as well as the expression level of Th1/Th2 cytokines with familial clustering of hepatocellular carcinoma ( HCC) to provide some evidence for the seeking susceptibility gene or resistant gene of HCC in Guangxi yao,China.Methods:With the same sexuality,age ±5 year,40 members whose families have had two or more HCC patients( high-occurrence families) were selected as the case group,and 40 members whose families have no any cancer patient were selected as the controls.Peripheral blood samples were collected to extract DNA,PCR-SSP was used to detect HLA-DQB1 alleles and ELISA was used to detect IL-2,IL-4 and IL-10.Results:(1) The gene frequency of the HLA-DQB1*02/09 alleles in the case group was higher than that in the controls(P0.05 ).( 2 ) The gene frequency of alleles HLA-DQB1 in HBsAg positive group and HBsAg negative group were never significant difference (P>0.05).(3)The expression levels of IL-4,IL-10 in the case group was higher than that in the control ( P<0.05 ).( 4 ) The expression level of IL-10 in the positive group of the HLA-DQB1*02 allele was higher than that in the negative group of the HLA-DQB1*02 allele ( P<0.05 ).( 5 ) The expression level of IL-4 in the positive group of the HLA-DQB1*09 allele was higher than that in the negative group of the HLA-DQB1*09 allele( P<0.05) .Con-clusion:(1) HLA-DQB1*02/09 seem to be susceptibility genes of hepatocellular carcinoma in high HCC incidence areas of Guangxi yao.(2) There may be not significant correlation bewteen HLA-DQB1 alleles and the susceptibility of HBV infection in high HCC incidence areas of Guangxi yao.( 3 ) The imbalance of IL-4, IL-10 might be associated with familial clustering of hepatocellular carcinoma in Guangxi yao.(4)The imbalance of IL-10 might be due to the carrying of HLA-DQB1*02;the imbalance of IL-4 might be due to the carrying of HLA-DQB1*09.Through the same approaches,these might lead to the phenomenon of familial aggregation of HCC in Guangxiyao.

A study of the frequencies of HLA-DQA1 alleles and their clinical application values in the donor-recipient HLA-10/10 matched hematopoietic stem cell transplantation / 中华微生物学和免疫学杂志

Objective To analyze the frequencies of HLA-DQA1 alleles and their clinical values in the donor-recipient HLA-A,-B,-C,-DRB1,-DQB1 (10/10) matched hematopoietic stem cell transplantation (HSCT).Methods This study recruited 127 patients who received allogeneic HSCT and 127 unrelated donors.High-resolution (High Res) DNA typing for HLA-DQA1 alleles were performed on the 254 subjects by using sequence specific oligonucleotide probes (SSOP) and high resolution of sequence specific primer(High Res SSP).Results The DQA1 allele genotypes of 36 pairs of donor-recipient were directly identified by using SSOP.The ambiguous DQA1 allele genotypes of the rest 91 pairs were identified by using High Res SSP.Among the 127 pairs of donor-recipient,5 pairs were HLA-DQA1 alleles mismatched,while the others were all matched.No significant differences in the distribution of HLA-DQA1 alleles were observed between the donors and the recipients.Sixteen HLA-DQA1 alleles were detected in the 127 donors,which were DQA1 * 02 ∶ 01 (19.3％),DQA1* 01 ∶ 02(19.3％),DQA1 * 03 ∶ 02/03 (17.0％),DQA1 *01∶03 (9.8％),DQA1*06∶01(9.1％),DQA1*05∶ 01(7.1％),DQA1*05∶05(5.9％),DQA1*03∶01 (4.7％),DQA1*01 ∶04(2.4％),DQA1*01∶05(2.0％),DQA1*01∶01(1.2％),DQA1*05 ∶ 03(0.8％),DQA1 *05 ∶ 08(0.8％),DQA1*04 ∶ 01(0.4％),DQA1*05 ∶ 06(0.4％) from high to low frequency.Moreover,a new allele was detected in the patients.The haplotypes' frequencies and linkage disequilibrium(LD) analysis of HLA-DQA1 and HLA-DQB1 showed that the most common haplotype was DQA1 *02 ∶ 01-DQB1 *02 ∶ 02(16.1％),followed by DQA1 *03 ∶ 02/03-DQB1 *03 ∶ 03 (11.8％)and DQA1 *01 ∶ 03-DQB1 * 06 ∶ 01 (9.1％).Stronger LD were observed between DQA1 * 02 ∶ 01 and DQB1*02 ∶ 02,DQA1 *03 ∶ 02 and DQB1*03 ∶ 03,DQA1 *01 ∶ 03 and DQB1*06 ∶ 01,HLA-DQA1*06∶01 andDQB1*03 ∶ 01,DQA1*05 ∶ 01 and DQB1*02 ∶ 02(P＜0.001).Conclusion There was strong linkage disequilibrium between HLA-DQA1 and HLA-DQB1 genes.The polymorphism of HLA-DQA1 gene was less than that of HLA-DQB1 gene.No more guidance was provided to donor selection in unrelated donor-recipient HLA matched HSCT by adding HLA-DQA1 genotyping,but it might have clinical application values in HSCT with HLA Ⅱ locus mismatched donor and recipient.

Performance of LIFECODES HLA-DQB1 Typing Kit Using Luminex Platform in Koreans

Intermediate-resolution HLA-DQ typing has gained importance in organ transplantation recently. We evaluated the performance of the LIFECODES HLA-DQB1 typing kit (Immucor, USA) using sequence-specific oligonucleotide (SSO) probe and Luminex platform (Luminex Corp., USA) on 100 samples tested by sequence-based typing (SBT) using the AlleleSEQR HLA-DQB1 kit (Abbott Molecular, USA) in Korean individuals. No sample showed ambiguity in the assignment of 4-digit HLA-DQB1 allele with the LIFECODES HLA-DQB1 SSO typing kit, and the results were fully concordant with those of high-resolution typing of AlleleSEQR HLA-DQB1 SBT up to 4-digit level. Three samples required adjustment of false reactions (3/100, 3.0%): two samples with DQB1*03:03/*06:01 showed false-positive result in probe 253, and 1 sample with DQB1*04:02/*05:02 showed false-negative result in probe 217. We tested an additional sample with DQB1*03:03/*06:01, which showed same false-positivity in probe 253 and 2 samples with DQB1*04:02/*05:02, which showed no false reaction. The false reactions did not result in ambiguity or change in the HLA allele assignment. We could assign HLA-DQB1 alleles to 4 digit-level without ambiguity, with 100% concordance with the SBT results. Thus, LIFECODES HLA-DQB1 SSO typing kit showed good performance for intermediate-resolution HLA-DQB1 typing in clinical laboratory for organ transplantation in Koreans.

Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre / Biomarcadores tradicionias em narcolepsia: experiência de um centro de sono brasileiro

This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG) and Multiple Sleep Latency Test (MSLT) were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF) was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N) - Hypocretin-1 higher than 110pg/ml and Lower (L) Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002). DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.

Este estudo foi idealizado para avaliar as características clinicas e laboratoriais de uma população de narcolépticos atendidos num centro de referência na cidade de São Paulo (Brasil). MÉTODO: 28 pacientes realizaram polissonografia e teste de múltiplas latências do sono segundo critérios internacionais. O alelo HLADQB1*0602 foi identificado por PCR. A Hipocretina-1 no líquido cefalorradiano (LCR) foi mensurada por radioimunoensaio. Os pacientes foram divididos em 2 grupos conforme o nível de Hipocretina-1. Normal (N) - Hypocretin-1 >110pg/ml e baixa (B) - Hypocretina-1 <110pg/ml. RESULTADOS: Somente 4 pacientes do grupo N tinham cataplexia quando comparados com 14 pacientes do grupo B (p=0,0002). DISCUSSÃO: Estes resultados foram comparáveis com outros autores, confirmando a utilidade do uso de biomarcadores específicos (HLA-DQB1*0602 e nível da hipocretina-1 no LCR) em narcolepsia com cataplexia. Porém, o alelo HLADQB1*0602 e a dosagem da Hipocretina-1 são insuficientes para o diagnóstico da narcolepsia sem cataplexia.

Prevalence of the HLA-DQB1*0602 allele in narcolepsy and idiopathic hypersomnia patients seen at a sleep disorders outpatient unit in São Paulo / Prevalência do alelo HLA-DQB1*0602 em pacientes com narcolepsia e hipersonolência idiopática atendidos em ambulatório de sonolência em São Paulo

OBJECTIVE: Narcolepsy (with and without cataplexy) and idiopathic hypersomnia, are disorders with common features but with different HLA-DQB1*0602 allele prevalence. The present study describes the prevalence of HLA-DQB1*0602 allele in narcoleptics with and without cataplexy and in patients with idiopathic hypersomnia. METHOD: Subjects comprised 68 patients who were diagnosed for narcolepsy or idiopathic hypersomnia and 23 healthy controls according to the International Classification of Sleep Disorders-2. Subjects comprised 43 patients with narcolepsy and cataplexy, 11 patients with narcolepsy but without cataplexy, 14 patients with idiopathic hypersomnia and 23 healthy controls. Genotyping of HLA-DQB1*0602 allele was performed for all subjects. RESULTS: The prevalence of the HLA-DQB1*0602 allele was increased in idiopathic hypersomnia and in narcoleptic patients with and without cataplexy when compared to healthy subjects (p = 0.04; p = 0.03 and p < 0.0001, respectively). CONCLUSIONS: This finding is in accordance with those of previous studies. The gold standard exam of narcolepsy with cataplexy is Hypocretin-1 dosage, but in patients without cataplexy and idiopathic hypersomnia, there are no specific diagnostic lab findings. The presence of the HLA-DQB1* 0602 allele may be important for the differential diagnosis of situations that resemble those sleep disorders such as secondary changes in sleep structure due to drugs' consumption.

OBJETIVO: Narcolepsia (com e sem cataplexia) e hipersonolência idiopática são transtornos com características clínicas comuns, mas com prevalências do alelo HLA-DQB1*0602 diferentes. Este estudo descreve a prevalência do alelo HLA-DQB1*0602 em pacientes narcolépticos com e sem cataplexia e em pacientes com hipersonolência idiopática. MÉTODO: A amostra consistiu de 68 pacientes com diagnóstico de narcolepsia ou hipersonolência idiopática e 23 controles saudáveis segundo o International Classification of Sleep Disorders-2. A amostra foi composta de 43 pacientes com narcolepsia e cataplexia, 11 pacientes com narcolepsia e sem cataplexia, 14 pacientes com hipersonolência idiopática e 23 controles saudáveis. A análise da presença do alelo HLA-DQ*0602 foi realizada em todos os sujeitos. RESULTADOS: A prevalência do alelo HLA-DQB1*0602 foi maior nos grupos de pacientes com hipersonolência idiopática e em pacientes narcolépticos com e sem cataplexia quando comparada com a dos sujeitos saudáveis (p = 0,04; p = 0,03 e p < 0,0001, respectivamente). CONCLUSÕES: Os resultados são compatíveis com o de estudos anteriores. O exame padrão-ouro para a confirmação da narcolepsia em pacientes com cataplexia é a dosagem de hipocretina, mas em pacientes sem cataplexia e hipersonolência idiopática não há testes laboratoriais específicos para o diagnóstico. A presença do alelo HLA-DQB1*0602 pode ser importante no diagnóstico diferencial de situações semelhantes a esses distúrbios do sono, como alterações secundárias na estrutura do sono causadas por consumo de drogas.

Influences of anxiety on humoral immune functions and the correlations with HLA-DQB1 / 中国免疫学杂志

Objective:To investigate the association between anxiety and the change of humoral immune functions and its correlation with HLA-DQB1 polymorphisms.Methods:Total 31 resident doctors were selected randomly and tested by State-Trait Anxiety Inventory(STAI).IgG,IgA,IgM,complement C3 and complement C4 were detected with BECKMAN array360 system;HLA-DQB1*02、*03、*04、*05 and*06 alleles were individually amplified by polymerase chain reaction(PCR)using exon2 group-specific primers.The correlation between immune function and HLA-DQB1 polgmorphisms were investigated.Results:Statistical analysis showed that there was positive correlation with State Anxiety (Ta) and complement C3,either Trait Anxiety (Tc) and complement C3.There was significant difference between HLA-DQB1*02 positive and negative in Ta (P＜0.05),while no difference in complement C3(P＞0.05).There was significant difference between HLA-DQB1*04 positive and negative in Ta and Tc(P＜0.05),while no difference in complement C3(P＞0.05).Conclusion:Anxiety could change some humoral immune functions and this is related with HLA-DQB1 polymorphism.

Prevalence of HLA DQB1*0602 allele in patients with migraine

BACKGROUND: Studies have shown a high prevalence of migraine among narcoleptic patients. HLA-DQB1*0602 and HLA DRB1 alleles are closely associated with narcolepsy. An increase in the HLA-DRB1 allele frequency in patients with visual aura has raised greater awareness of the genetic background in migraine. PURPOSE: Since the regions DR and DQ of the HLA are in tightly linkage desiquilibrium we hypothesize that HLA-DQB1*0602 might be associated to the pathophysiology of migraine. METHOD: We analyzed the presence of HLA DQB1*0602 allele in 50 healthy subjects with no history of migraine, 53 patients with migraine without aura and 52 patients with migraine with aura. RESULTS: There was no difference in the frequency of HLA DQB1*0602 allele when control subjects and all patients were compared. We failed to note any difference in frequencies when comparing migraine patients with and without aura. CONCLUSION: Further studies with different patient populations, with other hypothalamic markers (melatonin, hypocretin) in migraine patients may shed light on to its pathophysiology.

CONTEXTO: Estudos têm demonstrado o aumento da prevalência de enxaqueca em pacientes com narcolepsia, um distúrbio de sono associado a um gene do sistema HLA, o alelo HLA-DQB1*0602. As regiões DQ e DR do HLA estão em alto desequilíbrio de ligação e já foi descrito um aumento da freqüência do alelo HLA DRB1 em pacientes com enxaqueca com aura visual, o que fortalece uma hipótese de herança genética para a enxaqueca. OBJETIVO: Nossa hipótese é que o alelo HLA-DQB1*0602 pode estar relacionado com a fisiopatologia da enxaqueca destes pacientes. MÉTODO: Nós analisamos a presença do alelo HLA-DQB1*0602 em 50 voluntários sadios sem história de enxaqueca, 53 pacientes com enxaqueca sem aura e 52 pacientes com aura. RESULTADOS: Não houve diferença entre os controles sadios e os pacientes com enxaqueca. Não houve diferença entre os pacientes com enxaqueca com e sem aura. CONCLUSÃO: Futuros estudos com diferentes populações, com outros marcadores (melatonina e hipocretina) em pacientes com enxaqueca devem ser realizados para melhor esclarecimento de fisiopatologia.

Analysis of the markers related with relapse after withdrawal of antithyroid drug in patients with Graves' disease / 대한내과학회지

BACKGROUND: Graves' disease is an organ-specific autoimmune disease that is characterized by thyrotoxicosis, and this is caused by TSH receptor stimulating autoantibody. Antithyroid drugs have been a mainstay of treatment for Graves' patients. Unfortunately, over 50% of patients relapse after their first antithyroid drug treatment and the likelihood of remission cannot be foreseen. Some HLA genes are associated with disease susceptibility, but the association between HLA genes and relapse after drug withdrawal is unclear. In this study, we investigated the association between the HLA genes and the clinical parameters for predicting the clinical outcome of Graves' disease patients. METHODS: We enrolled the patients (n=191) with Graves' disease who were treated by antithyroid drug and who had previously undergone studies for their genetic susceptibility (HLA-DQB1, -DRB1). The success group included patients who maintained a euthyroid state for at least 12 months after withdrawal of drugs. The failure group was defined as the patients who relapsed within 1 year after discontinuation of drug or who could not discontinue their antithyroid drug treatment within 24 months. RESULTS: The rate of treatment failure was 75.4%. There was no significant association between the clinical outcome and the HLA genotyping. The genes that were associated with susceptibility to Graves' disease showed no association with the outcome. A few clinical parameters, such as male patients, severe thyrotoxicosis and high TSH-binding inhibitory immunoglobulin value were related to treatment failure. CONCLUSIONS: Genetic markers such as HLA-DQB1 and DRB1 can not be used, instead of the clinical parameters, to predict relapse after drug withdrawal.

HLA-DQB1 gene polymorphisms in Guangdong province detected by genechip / 第三军医大学学报

*0603.Conclusion The GF data of Chinese in Southern China are useful to correlation of diseases and anthropologic research.

Polymorphisms of HLA-DRB1 and -DQB1 Genes in Korean Patients with Pulmonary Tuberculosis / 결핵

BACKGROUND: It is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). METHODS: HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. RESULTS: Among the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was significantly increased in PTB patients (4.0% vs. 14.9%, p=0.004), showing similar increases in both DS and MDR cases. There was also an association of HLA alleles with the clinical severity of the disease according to the extent of lung lesion. Significantly increased frequencies of DRB1*08032 (4.2% vs. 32.6%, p=0.007) and DQB1*0601 (12.5% vs. 34.9%, p=0.047) were observed in more advanced (moderately & far advanced/DS and far advanced/MDR), compared with less advanced (minimal/DS and moderately advanced/MDR) lung lesions. Although DRB1*0701, DQB1*0202 and DQB1*0609 showed significant increases in different subsets of the disease, these HLA alleles did not show consistent association with disease severity. CONCLUSION: HLA-DRB1*08032 and DQB1*0601 alleles were associated with genetic susceptibility to MDR-TB in Korean patients, and also with disease severity and progression of PTB.

The genetic susceptibility of HLA-DRB1,-DQB1 alleles in esophageal squamous cell carcinoma / 中华消化杂志

Objective To probe into the association between the polymorphisms of HLA DRB1, DQB1 alleles and esophageal squamous cell carcinomas and then to further examine the features of their immunogenetics. Methods The polymorphisms of HLA DRB1, DQB1 alleles were typed by sequence specific primer based on polymerase chain reaction in 42 patients with esophageal squamous cell cancer and 136 normal control subjects. Results Allele frequency of HLA DRB1 *0901 allele was significantly higher in esophageal cancer patients than that in normal controls ( 0.250 0 vs 0.139 7 , P = 0.028 , odd ratio= 2.053 , etiologic fraction= 0.128 2 ) and so was allele frequency of HLA DQB1 * 0301 ( 0.297 6 vs 0.187 5 , P = 0.046 , odd ratio 1.835 , etiologic fraction 0.135 4 ). There was no association between the rested alleles of HLA DRB1 and DQB1 alleles in the patients. Conclusions Individuals carrying HLA DRB1 * 0901 and/or DQB1 * 0301 may be susceptible to esophageal squamous cell carcinoma, and nucleotide sequences of these two alleles were in accordance with the corresponded allele sequence (exon 2) of genebank.

HLA-DQA1, HLA-DQB1, and HLA-DRB1 Allele Frequency in Korean Patients with Schizophrenia / 신경정신의학

OBJECTIVE: The aim of this study was to investigate the correlation between HLA-DQA1, HLA-DQB1 and HLA-DRB1 alleles and disease susceptibility in Korean schizophrenic patients. METHODS: HLA-DQA1, HLA-DQB1, and HLA-DRB1 allele typing were performed using polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method in 128 Korean schizophrenic patients diagnosed by DSM-IV criteria, who were not blood-related, and 160 normal blood bank donors. RESULTS: The HLA-DQB1*04 allele frequency was 14.6% in schizophrenic patients, which was significantly higher than that of normal controls which was 8.2% (p=0.028). HLA-DRB1*14 allele frequency was 11.8% in patients, which was also more frequent than that of normal controls which was 5.5% (p=0.01). HLA-DRB*15 allele frequency was 2.0% in patients, which was significantly lower than that of normal controls which was 7.1% (p=0.007) and HLA-DRB*16 allele frequency was 1.6% in patients, which was also lower than that of normal controls which was 4.8% (p=0.043). CONCLUSIONS: Schizophrenia in Korea had positive correlation with HLA-DQB1*04 and HLA-DRB1*14, and negative correlation with HLA-DRB1*15 and HLA-DRB1*16. These findings support the association of the HLA-DQB1 and HLA-DRB1 with schizophrenia in Korean population, which was different from other study results in other different ethnic groups.

HLA-DQB1 allele frequencies and haplotypic associations with DRB1 genes in Koreans / 대한임상병리학회지

BACKGROUND: The HLA-DR and DQ genes are known to show in strong linkage disequilibrium. Authors investigated the allele frequencies of HLA-DQB1 genes and HLA-DQB1-DRB1 haplotypic associations in Koreans. METHODS: HLA-DRB1 and DQB1 typing were performed in 120 unrelated Koreans consisting of normal tissue donors and patients with hematologic diseases using polymerase chain reaction-reverse dot blot hybridization method with INNO-LiPA HLA-DRB and DQB kits (INNOGENETICS, Zwijndrecht, Belgium). Haplotypic associations between DRB1 and DQB1 alleles were calculated according to the formula from Mattiuz et al. RESULTS:1. Allele frequencies of the five most common DQB1 alleles were DQB1* 0301, 14.4%; 0303, 11.0%; 0302, 9.6%; 0601, 9.2%; 0401, 8.7%. 2. Haplotype frequencies (%) of the ten most common DQB1*-DRB1* haplotypes were 0303-0901, 9.17%; 0401-0405, 8.71%; 0602-1501/03/04, 7.35%; 0501-0101, 7.35%; 0601-0803, 5.98%; 0609-1302, 5.10%; 0503-1405, 4.69%; 0302-0406, 4.26%; 0301-1101/10/12 or 1104, 4.26%; 02-0701, 4.23%. They consisted 61.1% of total haplotypes in this study. CONCLUSIONS: The results of this study may be useful as basic data of Koreans for anthropology, accurate interpretaion of DRB1 and DQB1 typing and quality control of genotyping.