1.Study on the polymorphisme of human leucocyte antigen-DRB1, -DQA1 and -DQB1 alleles in patients with hepatitis B.
Chinese Journal of Epidemiology 2004;25(4):337-340
OBJECTIVETo investigate the association between the polymorphism of human leucocyte antigen (HLA)-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B.
METHODSHLA-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.
RESULTSThe 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).
CONCLUSIONHLA-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.
Adult ; Alleles ; DNA ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; HLA-DQ Antigens ; genetics ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hepatitis B ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic
2.Immunodeficiency Virus Type 1 Infection of H9 Cells.
Jeong Gu NAM ; Kyung Chang KIM ; Sue Kyong JEON ; Sung Soon KIM ; Sun Woo LEE ; Sung Whan AN ; Joo Shil LEE
Journal of Bacteriology and Virology 2004;34(1):57-66
Human immunodeficiency virus type 1 (HIV-1) virus causes severe defect in the immune system and affects the host cell gene expression profoundly. The gene expression pattern will be characterized by changes in cellular mRNA levels that are dependent on both the stage of infection and the biological state of the infected cells. The expression levels of 7,404 cellular RNA transcripts were assessed in H9 cells at different time points after HIV-1 IIIB infection. In total 7 time-points, 959/7,404 (13%) genes were a 2-fold or greater expressed. 387 of 959 genes (40.4%) were up-regulated, and other 572 genes (59.6%) were down-regulated. Three hundred seventeen genes were up-regulated a 2-fold or greater at 72 hr postinfection and 2 to 139 genes were up-regulated at the other time-points. In contrast, 126 to 349 genes were down-regulated a 2-fold or greater in all time-points, excepting 6 hr postinfection. Twenty-three genes were up-regulated a 2-fold or greater over at least four of seven time-points, which were mostly ribosomal proteins and MHCs. Especially, MHCs including HLA-DRA were steadily up-regulated from 24 hr postinfection. Thirty genes were down-regulated a 2-fold or greater in all the time-points, which were mainly related with synthesis and metabolism. These results show that host cell gene expression was altered by HIV-1 infection according to time-points and will provide a framework for studies on interactions between host and HIV-1 infection.
Gene Expression
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HIV-1
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HLA-DR alpha-Chains
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Immune System
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Metabolism
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Oligonucleotide Array Sequence Analysis
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Ribosomal Proteins
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RNA
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RNA, Messenger
3.Association of haplotype formed on HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection.
Liang-ping LU ; Xing-wang LI ; Ying LIU ; Guo-chang SUN ; Zhi-hai CHEN ; Xi-lin ZHU ; Quan-you HU ; Hui LI
Chinese Journal of Medical Genetics 2006;23(4):427-430
OBJECTIVETo 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.
METHODSTwo 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).
RESULTSThe 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).
CONCLUSIONIndividuals with different haplotypes composed of HLA-DRB1 and HLA-DQA1 might have different outcomes of HBV infection.
Adolescent ; Adult ; Alleles ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; HLA-DQ Antigens ; genetics ; HLA-DQ alpha-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Haplotypes ; Hepatitis B ; genetics ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction
4.Comparative study of HLA-DQA1 and HLA-DRB1 allele in patients with endometriosis and adenomyosis.
Lili ZONG ; Dejing PAN ; Weiming CHEN ; Yuanli HE ; Zehuan LIU ; Jianghai LIN ; Anlong XU
Chinese Journal of Medical Genetics 2002;19(1):49-51
OBJECTIVETo make a comparative study of HLA-DQA1 and HLA-DRB1 allele frequencies in the cases of endometriosis and adeonmyosis.
METHODSThe allelic types of HLA-DQA1 and HLA-DRB1 were detected by polymerase chain reaction-sequence specific primers (PCR-SSP) technique in 51 cases of endometriosis, 45 cases of adenomyosis, and 44 normal individuals as the control.
RESULTSThe frequencies of HLA-DQA1*0401(7.8%, 10.0%) were significantly increased in the endometriosis group and the adenomyosis group (Pc=0.03, Pc=0.01), and the frequencies of HLA-DQA1*0301(8.8%, 5.6%) were significantly decreased in these two groups (Pc=0.00, Pc=0.00).There was no significant difference between the frequencies of HLA-DQA1 and HLA-DRB1 of endometriosis and adenomyosis.
CONCLUSIONThe results indicate that HLA-DQA1*0301 and *0401 alleles are associated with both endometriosis and adenomyosis, and there is perhaps common mechanism involved in both endometriosis and adenomyosis based on HLA-DQA1 and HLA-DRB1 allele frequencies.
Asian Continental Ancestry Group ; genetics ; Endometriosis ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; HLA-DQ Antigens ; genetics ; HLA-DQ alpha-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Humans ; Polymerase Chain Reaction ; methods
5.Effects of HCV genotypes and HLA-DRB alleles on the response of chronic hepatitis C patients to interferon alpha and libavilin.
Chinese Journal of Hepatology 2003;11(10):620-622
OBJECTIVESTo study the effects of HCV genotypes and HLA-DRB alleles on the response of chronic hepatitis C patients to interferon alpha and libavilin.
METHODSGenotypes of HCV in 113 patients with HCV infection treated with interferon alpha and libavilin were investigated. Gene chips were used to analyze the frequency of HLA-DRB alleles in 25 patients of them. The response to interferon alpha and libavilin therapy were discussed.
RESULTSThe response rates in the four HCV types were different, HCV-IV/2b the highest (57.78%), HCV-I/1a and -III/2a lower (46.15% and 47.62%), and HCV-II/1b the lowest (11.76%). The response rate to IFN and libavilin therapy in patients with DRB1*07 positive was higher, while in patients with DRB1*04 positive was lower. Sex, HCV genotypes and HLA-DRB alleles were all related to the response. Female, patients with HCV-IV/2b and HLA-DRB1*07 presented almost complete response, but male, patients with HCV-II/1b and HLA-DRB1*04 usually appeared non-response. DRB1*07 allele and HCV-IV/2b were the closest factors related to the response.
CONCLUSIONSNot only virus but also host playes an important role in the curative effect of anti-virus therapy. It is necessary to view from the angle of host, adjusting the host's immune status to accelerate the clearance of HCV.
Adult ; Alleles ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; drug therapy ; immunology ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Ribavirin ; therapeutic use
6.The relationship between alpha-IFN anti-virus treatment and HLA-DRB1*11 gene mononucleotide polymorphism.
Jia-bao CHANG ; Zhen-xian ZHOU ; Rong XUE ; Guan-shan ZHU ; Yu-ling TIAN ; Wei ZHAO
Chinese Journal of Hepatology 2008;16(9):646-648
OBJECTIVETo investigate the relationship between the distribution of mononucleotide polymorphism of five regulation regions of alpha-IFN among HLA-DRB1*11 gene episodes and the therapeutic effects of alpha-IFN treatment in chronic hepatitis B patients.
METHODSOne hundred seven chronic hepatitis patients from Nanjing Second Hospital who were treated by alpha-IFN for 12 months and then followed at least six months without the treatment were randomly selected for this regressive analysis. They were grouped into a continuous responsive group and a non-continuous responsive group. Hepatitis B virus X interacting protein gene locus was searched in NCBI. Single nucleotide polymorphism (SNP) gene locus was detected based on a pooling sequencing method. Primer and TaqMan-MGB probes referring to different mononucleotide loci were designed respectively to detect SNP in five regulation regions of alpha-IFN. Then gene sequencing differences between the two groups were analyzed.
RESULTSAmong the 107 cases there were 30 cases (28.0%) in the continuous responsive group and 77 cases (71.9%) in the non-continuous responsive group. CT occupation rate in five regulation regions of IFN reached 18.0% in the continuous responsive group and 23.8% in the non-continuous responsive group. AG occupation rate reached 10.8% in the former group and 15.8% in the latter group. The differences in CT and AG between the two groups were significant.
CONCLUSIONSThe distribution of mononucleotide polymorphism of five regulation regions of alpha-IFN among HLA-DRB1*11 gene episodes affects the IFN anti-virus treatment. Detecting the gene distribution of mononucleotide in five regulation regions of alpha-IFN helps in predicting the therapeutic effects of alpha-IFN.
Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; DNA, Viral ; Genotype ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; genetics ; Humans ; Interferon-alpha ; therapeutic use ; Polymorphism, Single Nucleotide ; Regression Analysis ; Treatment Outcome ; Young Adult
7.Association of polymorphisms of human leucocyte antigen -DRB1 and -DQA1 allele with outcomes of hepatitis B virus infection in Han population of north China.
Liang-ping LU ; Ying LIU ; Xing-wang LI ; Guo-chang SUN ; Xi-lin ZHU ; Yun-zhong WU ; Quan-you HU ; Hui LI
Acta Academiae Medicinae Sinicae 2006;28(2):134-142
OBJECTIVETo 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.
METHODSA 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.
RESULTSThe 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)
CONCLUSIONSThe 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.
Adolescent ; Adult ; Alcohol Drinking ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Environment ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; HLA-DQ Antigens ; genetics ; HLA-DQ alpha-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hepatitis B ; ethnology ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Risk Factors
8.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.
Shulan HE ; Wuhong TAN ; Sen WANG ; Cuiyan WU ; Pan WANG ; Bin WANG ; Xiaohui SU ; Junjie ZHAO ; Xiong GUO ; Youzhang XIANG
Chinese Medical Journal 2014;127(1):72-78
BACKGROUNDKeshan 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.
METHODSWe 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.
RESULTSAmong 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.
CONCLUSIONOur results might help to explain the higher susceptibility of women to this disease.
ADAM Proteins ; genetics ; ADAMTS Proteins ; Adult ; Autoimmunity ; genetics ; physiology ; Bone Morphogenetic Protein 5 ; genetics ; Bone Morphogenetic Protein 7 ; genetics ; Cardiomyopathies ; genetics ; pathology ; Cell Differentiation ; genetics ; physiology ; Chemokines, CC ; genetics ; Enterovirus Infections ; genetics ; pathology ; Female ; Gene Expression Profiling ; HLA-D Antigens ; genetics ; HLA-DQ alpha-Chains ; genetics ; HLA-DR alpha-Chains ; genetics ; Humans ; Male ; Middle Aged ; Myocytes, Cardiac ; cytology ; metabolism ; Oligonucleotide Array Sequence Analysis ; Sex Factors ; Tumor Necrosis Factor Ligand Superfamily Member 15 ; genetics