福建地区乙型肝炎肝硬化与人类白细胞抗原DRB1基因的相关性

目的:研究人类白细胞抗原(human leucocyte antgen,HLA)-DRB1基因多态性与福建汉族人乙型肝炎肝硬化的遗传易感性关系.方法:以93例福建地区汉族人群乙型肝炎肝硬化患者为研究对象,以同一地区84例健康人为对照人群,采用DNA测序分型技术(sequencing-based typing,SBT)对HLA-DRB1等位基因精确分型,计算各组等位基因频率,对照人群等位基因分布进行Hardy-Weinberg遗传平衡检验.应用遗传统计方法进行关联分析,确定与乙型肝炎肝硬化相关的易感基因及基因型.结果:乙型肝炎肝硬化组HLA-DRB1*04等位基因频率明显高于对照组(OR=2.536,95%CI:1.292-4.978,P=0.0068).HLA-DRB1*1101等位基因频率明显低于对照组(OR=0.339.95%CI:0.119-0.964,P=0.0425);HLA-DRB1 04基因型在病例组与对照组之间分布差异具有统计学意义(OR=3.456,95%CI:1.553-7.692,x2=9.227,P=0.0024),乙型肝炎肝硬化与HLA-DRB 04基因型剂量线性相关(OR=2.457,95%CI:1.274-4.737,x2=7.197,P=0.0073).结论:HLA-DRB1*04主型等位基因及其基因型可能是乙型肝炎肝硬化的易感基因,HLA-DRBI*1101等位基因可能为其抗性基因.     

中国人群XRCC1 Arg399Gln基因多态性与肝癌易感性Meta分析

目的:系统评价中国人群X线修复交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)Arg399Gln基因多态性与肝癌易感性的关系.方法:在Pub Med、MEDLINE、EMBASE、CNKI、CBM、VIP及万方数据库中检索2000-01-01/2015-01-10发表的所有有关中国人群XRCC1 Arg399Gln基因多态性与肝癌易感性关系的相关文献.按照纳入和排除标准独立选择文献、提取资料,采用Stata12.0软件进行Meta分析,计算合并比值比(odds ratio,OR)及其95%可信区间(95%confidence interval,95%CI),并进行敏感性分析和发表偏倚的估计.结果:按照入选标准,共纳入13个研究,包括2972例患者和3789例对照者.Meta分析结果显示,与基因型Arg/Arg、Arg/Arg+Arg/Gln分别进行比较,基因型Gln/Gln均增加中国人群罹患肝癌风险(OR=1.47,95%CI:1.24-1.74,P0.001;O R=1.26,95%C I:1.08-1.48,P=0.003);与基因型Arg/Arg进行比较,基因型Gln/Gln+Arg/Gln增加中国人群罹患肝癌风险(OR=1.49,95%CI:1.21-1.83,P0.001).与等位基因Argalele比较,等位基因Gln-allele增加中国人群罹患肝癌的风险(OR=1.33,95%CI:1.16-1.54P0.001).结论:XRCC1 Arg399Gln基因多态性与中国人群肝癌易感性相关,基因型Gln/Gln增加中国人群罹患肝癌的风险.     

HLA-DRB1等位基因多态性对食管癌发生影响的Meta分析

目的采用系统评价的方法探究HLA-DRB1等位基因多态性对于食管癌发生的影响。方法计算机检索Medline、EMbase、Cochrane Library、Web of Science、CBM、CNKI、VIP、万方等数据库查找相关文献。按照纳入和排除标准筛选后提取数据,采用Stata12.0软件进行Meta分析。结果最终纳入5篇文献,总共包含1 630例患者。Meta分析结果显示,食管癌组HLADRB1*0901基因易感率明显高于正常人,两组基因易感率差异有统计学意义[OR=1.70,95%CI(1.31,2.20),P0.001];食管癌患者HLA-DRB1*1501基因易感率明显高于正常人,两组基因易感率差异有统计学意义[OR=3.02,95%CI(1.65,5.51),P0.001];食管癌组HLA-DRB1*0301基因易感率明显高于正常人,两组基因易感率差异有统计学意义[OR=2.84,95%CI(0.43,18.96),P0.001]。结论食管癌的发生与HLA-DRB1*0901、HLA-DRB1*1501与HLA-DRB1*0301基因有关。     

HBV感染者人类白细胞Ⅰ,Ⅱ类抗原等位基因多态性分析

目的:分析HBV感染者体内病毒持续和清除与HLA-A,B,DRB1各位点等位基因分布频率的关系.方法:采用序列特异性引物-聚合酶链式反应(PCR-SSP)技术,对61例慢性乙型肝炎患者(CHB)、32例HBV感染后病毒清除者(感染恢复组)和40例骨髓移植供者(正常组)的外周血白细胞,进行人类白细胞抗原等位基因(HLA-A,B,DRB1)分型检测.结果:在慢性乙型肝炎组,HLA-DRB1*12等位基因分布频率较正常组(0.230vs0.075,P=0.004,OR=3.674,95%CI:1.445-9.338)和HBV感染恢复组(0.230vs0.063,P=0.004,OR=4.468,95%CI:1.492-13.377)均显著增高,HLA-B*35,DRB1*13则显著降低(0.066vs0.163,P=0.027,OR=0.362,95%CI:0.143-0.918;0.016vs0.008,P=0.017,OR=0.174,95%CI:0.035-0.859);HLA-A*69,B*56也显著降低(均0.000vs0.037,P=0.031).HLA-A*02等位基因分布频率在慢性肝炎组与HBV感染恢复组比较显著降低(P=0.044),HLA-B*51在感染恢复组与正常组比较显著增高(P=0.019).结论:机体对HBV易感性和病毒持续或清除与HLA等位基因多态性相关.HLA-DRB1*12可能既为易感性位点,又能促进病毒的持续感染;HLA-B*51,A*02可能为易感性位点,但感染后易清除病毒;HLA-DRB1*13可能是抗HBV感染的保护性基因;HLA-B*35,B*56和A*69在中国北方汉族人可能也为抗HBV感染的保护性基因.     

中国汉族人群基质金属蛋白酶9基因-1562C>T多态性与冠心病易感性的Meta分析

目的综合评价中国汉族人群基质金属蛋白酶9基因-1562C>T多态性与冠心病易感性相关。方法通过文献检索收集2010年12月以前完成或发表的中国汉族人群基质金属蛋白酶9基因-1562C>T多态性与冠心病相关性的病例对照研究,剔除不符合要求的文献,以漏斗图检验入选文献的偏倚,并根据各入选文献结果的同质性检验结果进行数据合并,计算总OR值,Meta分析采用Revman5.0及StatalO.0统计软件。结果共7篇文献符合条件纳入研究,入选文献无明显偏倚,Meta分析显示TT+CT基因型比CC基因型OR=1.47(95%CI为1.20～1.78,P=0.0001);T等位基因比C等位基因OR=1.41(95%CI为1.17～1.69,P=0.0002);CC基因型比CT+TT基因型OR=0.68(95%CI为0.55～0.82,P<0.0001);CT基因型比CC+TT基因型OR=1.45(95%CI为1.19～1.77,P=0.0002)。结论基质金属蛋白酶9基因-1562C>T多态性与中国汉族人群冠心病易感性相关,T等位基因可能是冠心病遗传危险因素。     

XPA基因A23G多态性与食管癌易感性的Meta分析

目的:探讨人类着色素干皮病基因(xeroderma pigmentosum group A,XPA)A23G多态性与食管癌易感性的关系.方法:计算机检索Pub Med、EMBASE、The Cochrane Library、Web of Science、中国生物医学数据库、万方数据库、中国期刊全文数据库、中文科技期刊数据库多个数据库,收集XPA基因A23G多态性与食管癌易感性的病例-对照研究.根据纳入与排除标准筛选符合标准的文献,提取数据并进行质量评价,采用STATA12.1统计软件进行Meta分析.结果:符合入选标准的9个病例-对照研究,其中实验组食管癌患者2065例,对照组非肿瘤患者3552例.Meta分析结果显示:XPA基因A23G位点多态性的等位基因模型、显性基因模型、隐性基因模型及相加基因模型与食管癌罹患风险无相关性,分别为:(OR=1.0 1,9 5%CI:0.7 6-1.3 4)、(OR=0.8 7,9 5%CI:0.6 1-1.2 3)、(OR=0.9 7,95%CI:0.66-1.42)、(O R=1.12,95%CI:0.65-1.92),但共显性基因模型与罹患食管癌的风险增高有统计学相关性(OR=1.20,95%CI:1.07-1.35).根据种族进行亚组分析显示:亚洲人群共显性基因模型与罹患食管癌的风险增高有统计学相关性(OR=1.25,95%CI:1.10-1.44),其余基因模型无统计学意义,高加索人群食管癌易感性与各遗传基因模型均无统计学意义(P0.05).根据对照组纳入人群进行亚组分析显示:对照组来源人群的共显性基因模型与罹患食管癌的风险增高有统计学相关性(OR=1.26,95%CI:1.08-1.48),其余基因模型无统计学意义,对照组来源于医院的人群食管癌易感性与各遗传基因模型均无统计学意义(P0.05).结论:XPA A23G基因多态性的等位基因、显性基因模型、隐性基因模型、相加基因模型与食管癌易感性可能无相关性,共显性基因模型与食管癌易感性可能有相关性.     

内皮型一氧化氮合酶基因a/b多态性与中国人群糖尿病肾脏疾病易感性的Meta分析

目的基于Meta分析方法探讨内皮型一氧化氮合酶(eNOS)基因a/b多态性与中国人群DKD的相关性。方法全面检索数据库,收集有关eNOS基因a/b多态性与中国人群DKD易感性的文献,对符合条件的研究结果应用RevMan 5.2和STATA 12.0软件进行统计分析。结果共纳入10篇文献,包含病例组(DKD)1079例和对照组(T2DM)796例。Meta分析结果表明,eNOS基因a/b多态性与中国人群DKD密切相关[aavs bb:OR=2.02,95%CI 1.12～3.64,P=0.02;ab vs bb:OR=1.77,95%CI1.15～2.73,P=0.01;aavs(ab+bb):OR=1.99,95%CI 1.12～3.57,P=0.02;(aa+ab)vs bb:OR=1.97,95%CI1.29～3.00,P=0.002;avs b:OR=1.88,95%CI 1.23～2.86,P=0.003]。敏感性分析提示结论稳定性好。结论 eNOS基因a/b多态性与中国人群DKD的发生发展相关;等位基因a可能是中国人群DKD的易感基因。     

TNF-α基因G-308A多态性与中国人原发性高血压相关性的Meta分析

目的评价肿瘤坏死因子α(TNF-α)基因G-308A多态性与中国人原发性高血压(essential hypertension,EH)的相关性。方法计算机检索PubMed、EMbase、CBM、CNKI和万方数据库,收集关于TNF-α基因G-308A多态性与中国人EH相关性的病例-对照研究,检索时限均为建库至2013年9月1日。由2位评价者严格按照纳入与排除标准独立筛选文献、提取资料及质量评价后,采用Stata12.0软件进行Meta分析。采用Egger线性回归法检测发表偏倚。结果最终纳入6个病例-对照研究,包括EH患者1203例和健康对照1354例。Meta分析结果显示:对于中国人群,基因型GA人群的EH发病风险高于基因型GG人群(OR=1.54,95%CI:1.23~1.92,P0.001);基因型AA+GA人群的EH发病风险高于基因型GG人群(OR=1.59,95%CI:1.28~1.98,P0.001);等位基因A人群的EH发病风险高于等位基因G人群(OR=1.58,95%CI:1.29~1.95,P0.001)。结论中国人群TNF-α基因G-308A等位基因A与EH发病有关。受纳入研究数量及质量限制,上述结论尚待开展进一步研究加以验证。     

白细胞介素1A基因3'-UTR I/D多态性与中国汉族人群癌症易感性的Meta分析

目的综合分析白细胞介素(IL)1A基因rs3783553单核苷酸多态性与中国汉族人群癌症易感性的关系。方法检索Pubmed、Springer、EMBASE以及中国知网、万方和生物医学文献数据库,检索有关IL-1A基因rs3783553位点多态性与癌症易感性的病例对照研究,利用STATA12.0软件行Meta分析,并进一步行亚组分析、敏感性分析及发表偏倚检测。结果本研究共纳入14篇文献,共计12 369例研究对象,其中癌症患者5 708例,健康对照者6 661例。Meta分析结果显示,等位基因模型I vs.D(OR=0.82,95%CI:0.75~0.89)、纯合子模型II vs.DD(OR=0.62,95%CI:0.55~0.70)、杂合子模型ID vs.DD(OR=0.86,95%CI:0.80~0.93)、隐性基因模型II vs.ID/DD(OR=0.68,95%CI:0.60~0.76)以及显性基因模型II/ID vs.DD(OR=0.81,95%CI:0.75~0.87)中各基因型的癌症易感性差异均存在统计学意义(P均<0.05)。亚组分析结果显示,该基因位点多态性可能与我国汉族人群罹患消化系统恶性肿瘤以及女性罹患生殖系统癌症的风险降低有关。结论 IL-1A基因rs3783553多态性与中国汉族人口癌症易感性相关,其中I等位基因可能是中国汉族人群的保护因素,而等位基因D则可能是其癌症易感因素。     

MTHFR基因1298A>C位点多态性与亚洲人群乳腺癌易感性的Meta分析

目的采用Meta分析评价MTHFR基因1298AC位点多态性与亚洲人群乳腺癌发病风险的相关性。方法计算机检索PubMed、EMBASE、web of science、中国生物医学文献数据库、CNKI数据库、VIP数据库和万方数据库,搜集国内外关于MTHFR基因1298AC位点多态性与乳腺癌易感性的病例对照研究,检索时限均为建库至2016年8月。由2位研究者独立进行文献筛选及资料提取,采用Stata12. 0软件行Meta分析。结果最终纳入17个病例对照研究,包括5 680例乳腺癌患者,6 403例对照。Meta分析结果显示:对于亚洲人群,MTHFR基因1298AC位点多态性与亚洲人群乳腺癌发病风险无相关性[AA vs AC:OR=1. 07,95%CI(0. 99～1. 15),P=0. 653; AC vs CC:OR=0. 89,95%CI(0. 76～1. 05),P=0. 891; AA vs CC:OR=0. 92,95%CI(0. 79～1. 08),P=0. 906; AA vs AC+CC:OR=1. 05,95%CI(0. 97～1. 13),P=0. 630; AA+AC vs CC:OR=0. 92,95%CI(0. 79～1. 07),P=0. 905]。结论MTHFR基因1298AC位点多态性不增加亚洲人群乳腺癌的发病风险。     

Relationship of human leukocyte antigen class Ⅱ genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients.METHODS: Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B (CHB) and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai.Among CHB patients, 35 were treated with IFNα-1b for 24 wk.RESULTS: The frequencies of HLA-DRB1*06, DRB1*08and DRB1*16 alleles in 72 patients were higher than in 200 healthy people (2.08% vs0%, OR = 3.837, P= 0.018;11.11% vs5.50%, OR = 2.148, P= 0.034; and 6.94% vs 3.00%, OR = 0.625, P = 0.049, respectively); whereas that of DRB1*07 allele was lower (2.78% vs 7.75%,OR = 0.340, P = 0.046). The frequency of HLA-DRB1* 14allele was higher in 11 responders to IFN compared with 24 non-responders (18.18% vs2.08%, OR = 10.444,P = 0.031), whereas that of DQB1*07 allele was inverse (9.09% vs 37.50%, OR = 0.167, P= 0.021).CONCLUSION: The polymorphism of HLA class Ⅱ may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRB1*06, DRB1*08, and DRB1*16 may be associated with chronicity of HBV infection, HLA-DRB1*07 with protection against HBV infection, and HLA-DRB1*14 allele may be associated with a high rate of the response of CHB patients to IFN treatment.Compared with other HLA-DQB1 alleles, HLA-DQB1*07 may be associated with low response rate to IFN.     

Relationship of human leukocyte antigen class Ⅱ genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients. METHODS: Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B (CHB) and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai. Among CHB patients, 35 were treated with IFNa-lb for 24 wk. RESULTS: The frequencies of HLA-DRB1~*06, DRB1~*08 and DRB1~*16 alleles in 72 patients were higher than in 200 healthy people (2.08% vs0%, OR=3.837, P=0.018; 11.11% vs 5.50%, OR=2.148, P=0.034; and 6.94% vs 3.00%, OR=0.625, P=0.049, respectively); whereas that of DRB1~*07 allele was lower (2.78% vs 7.75%, OR=0.340, P=0.046). The frequency of HLA-DRB1~*14 allele was higher in 11 responders to IFN compared with 24 non-responders (18.18% vs 2.08%, OR=10.444, P=0.031), whereas that of DQB1*07 allele was inverse (9.09% vs 37.50%, OR=0.167, P=0.021). CONCLUSION: The polymorphism of HLA class II may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRB1~*06, DRB1~*08, and DRB1~*16 may be associated with chronicity of HBV infection, HLA-DRB1~*07 with protection against HBV infection, and HLA-DRB1~*14 allele may be associated with a high rate of the response of CHB patients to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQB1~*07 may be associated with low response rate to IFN.     

HLA-DRB1*09/12/15与广西HBV相关性肝病的关系

目的:探讨HLA-DRB1*09/12/15等位基因频率与广西乙型肝炎病毒(hepatitis B virus,HBV)相关性肝病病情的关系.方法:应用聚合酶链反应-序列特异性引物(polymerase chain reaction-sequence specific primer,PCR-SSP)技术对64例慢性无症状HBV携带者(asymptomatic chronic hepatitis B,ASC)组、80例慢性乙型肝炎(chronic hepatitis B,CHB)组、65例乙肝肝硬化(liver cirrhosis,LC)组、56例乙肝肝细胞癌(hepatocellular carcinoma,HCC)组以及75例正常对照(NC)组的HLA-DRB1*09/12/15等位基因进行检测,分析其表达频率与慢乙肝病情的相关性.结果:乙肝肝硬化组HLA-DRB1*15等位基因的携带率(10.8%),较NC组(34.7%)、ASC组(39.1%)、HCC组(33.9%)、CHB组(33.8%)明显减低,差异具有统计学意义(P<0.01),其余各组两两比较均无统计学差异;HLA-DRB1*09/12在各组间的分布均无统计学差异.结论:HLA-DRB1*15等位基因携带者感染HBV后可能降低乙肝肝硬化发生的风险,HLA-DRB1*15可能是广西乙肝肝硬化的抵抗基因.     

No primary association of MICA polymorphism with systemic lupus erythematosus

OBJECTIVE: To replicate the described association between MHC class I chain-related A (MICA) gene polymorphism and susceptibility to systemic lupus erythematosus (SLE). METHODS: MICA transmembrane microsatellite polymorphism was genotyped using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B* and DRB1* was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probe system. Combined data for these three loci (HLA-B*, DRB1* and MICA) were obtained from a total of 333 patients and 361 healthy controls. RESULTS: Significant association with B*08 [P < 10(-7), odds ratio (OR) 3.17, 95% confidence interval (CI) 2.02-5.00], DRB1*0301 (P < 10(-7), OR 2.07, 95% CI 1.59-2.68) and MICA5.1 (P = 0.01, OR 1.23, 95% CI 1.04-1.46) was observed. The combinations DRB1*0301-MICA5.1-B8 and HLA-DRB1*0301-B*08-positive and MICA5-1-negative were more frequent among SLE patients (11.4 vs 3.3% in healthy controls, P = 3.9 x 10(-5), OR 3.76, 95% CI 1.85-7.73, and 6.9 vs 1.7%, P = 0.0007, OR 4.32, 95% CI 1.68-13.10, respectively). Additionally, individuals who were HLA-DRB1*0301-B*08-negative and MICA5-1-positive were less frequent among patients (22.2 vs 31.3% in healthy controls, P = 0.007, OR 0.63, 95% CI 0.44-0.89) and the magnitude of the OR was similar to that obtained in individuals negative for all the three factors (OR 0.69, 95% CI 050-0.94). Further analysis performed to detect independent association strongly suggested that the association between MICA5.1 and SLE is secondary to the linkage disequilibrium of this allele with B*08. CONCLUSIONS: Our results do not support an independent association of MICA gene polymorphism with susceptibility to SLE.     

Relationship between HLA-DR gene polymorphisms and outcomes of hepatitis B viral infections: a meta-analysis

AIM: To assess the rigorous relationship between human leukocyte antigens (HLA)-DR alleles and outcomes of hepatitis B virus (HBV) infections by means of meta-analysis.METHODS: Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Study quality was evaluated using the Newcastle-Ottawa Scale. Odds ratios (OR) and 95% confidence interval (95% CI) were pooled using Stata 11.0. Subgroup analyses were performed by ethnicity. Heterogeneity and publication bias analyses were performed to validate the credibility.RESULTS: A total of 2609 patients with chronic hepatitis B and 2606 controls spontaneously recovering from prior HBV infection were included. Meta-analysis showed that HLA-DR*04 (OR = 0.72, 95% CI: 0.60-0.85) and DR*13 (OR = 0.27, 95% CI: 0.19-0.37) alleles were significantly associated with HBV clearance while patients carrying HLA-DR*03 (OR = 1.47, 95% CI: 1.16-1.87) or DR*07 (OR = 1.59, 95% CI: 1.24-2.03) alleles had a significantly increased risk of chronic HBV persistence. For the HLA-DR*01 polymorphism, a significantly association with HBV clearance was found in Chinese Han group (OR = 0.48, 95% CI: 0.26-0.86), but not found in other ethnic groups (P = 0.191). For other polymorphisms, no association with the HBV infection outcome was found.CONCLUSION: HLA-DR*04 and DR*13 alleles may be the protective factors for HBV clearance and HLA-DR*03, and DR*07 alleles may be the risk factors for HBV persistence.     

MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility

OBJECTIVES: Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA. METHODS: A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism -62 of the IkappaBL gene. RESULTS: A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) = 0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between IkappaBL and MICA with RA was found. CONCLUSIONS: MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.     

Association between HLA class Ⅱ gene and susceptibility or resistance to chronic hepatitis B

AIM: To investigate the association between the polymorphism of HLA-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B.METHODS: HLA-DRB1, -DQA1 and -DQB1 alleles in 54patients with chronic hepatitis B, 30 patients with acute hepatitis B and 106 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique.RESULTS: The allele frequency of HLA-DRB1*0301 in the chronic hepatitis B group was markedly higher than that in the normal control group (17.31% VS 5.67%), there was a significant correlation between them (χ2= 12.3068,Pc=0.0074, RR=4.15). The allele frequency of HLADQA1*0501 in the chronic hepatitis B group was significantly higher than that in the normal control group (25.96% VS 13.68%), there was a significant correlation between them (χ2=9.2002, PC＝0.0157, RR=2.87). The allele frequency of HLA-DQB1*0301 in the chronic hepatitis B group was notably higher than that in the normal control group (35.58%vs 18.87%), there was a significant correlation between them (χ2=15.5938, PC=0.0075, RR=4.07). The allele frequency of HLA-DRB1*1101/1104 in the chronic hepatitis B group was obviously lower than that in the normal control group (0.96% VS 13.33%), there was a significant correlation between them (χ2=11.9206, PC=0.0145, RR=18.55). The allele frequency of HLA-DQA1*0301 in the chronic hepatitis B group was remarkably lower than that in the normal control group (14.42% VS30%), there was a significant correlation between them (χ2=8.7396, Pc=0.0167, RR=0.35).CONCLUSION: HLA-DRB1*0301, HLA-DQA1*0501 and HLA-DQB1*0301 are closely related with susceptibility to chronic hepatitis B, and HLA-DRB1*1101/1104 and HLADQA1*0301 are closely related with resistance to chronic hepatitis B. These findings suggest that host HLA class Ⅱ gene is an important factor determining the outcome of HBV infection.     

Association between HLA class Ⅱ gene and susceptibility or resistance to chronic hepatitis B

AIM: To investigate the association between the polymorphism of HLA-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B. METHODS: HLA-DRB1, -DQA1 and -DQB1 alleles in 54 patients with chronic hepatitis B, 30 patients with acute hepatitis B and 106 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique. RESULTS: The allele frequency of HLA-DRB1*0301 in the chronic hepatitis B group was markedly higher than that in the normal control group (17.31% vs 5.67 %), there was a significant correlation between them (X^2= 12.3068,PC=0.0074, RR=4.15). The allele frequency of HLA-DQAI*0501 in the chronic hepatitis B group was significantly higher than that in the normal control group (25.96 % vs 13.68 %), there was a significant correlation between them (X^2=9.2002, PC=0.0157, RR=2.87). The allele frequency of HLA-DQBI*0301 in the chronic hepatitis B group was notably higher than that in the normal control group (35.58 % vs 18.87 %), there was a significant correlation between them (x^2=15.5938, PC=0.0075, RR=4.07). The allele frequency of HLA-DRB1*1101/1104 in the chronic hepatitis B group was obviously lower than that in the normal control group (0.96 % vs 13.33 %), there was a significant correlation between them (X^2=11.9206, PC=0.0145, RR=18.55). The allele frequency of HLA-DQAI*0301 in the chronic hepatitis B group was remarkably lower than that in the normal control group (14.42 % vs30 %), there was a significant correlation between them (X^2=8.7396, PC=0.0167, RR=0.35). CONCLUSION: HLA-DRBI*0301, HLA-DQAI*0501 and HLA-DQBI*0301 are closely related with susceptibility to chronic hepatitis B, and HLA-DRB1*1101/1104 and HLA-DQAI*0301 are closely related with resistance to chronic hepatitis B. These findings suggest that host HLA class Ⅱ gene is an important factor determining the outcome of HBV infection.     

HLA-DRB4 as a genetic risk factor for Churg-Strauss syndrome

OBJECTIVE: To explore the association between HLA alleles and Churg-Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease. METHODS: Low-resolution genotyping of HLA-A, HLA-B, and HLA-DR loci and genotyping of TNFA -238A/G and TNFA -308A/G single-nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls. RESULTS: The frequency of the HLA-DRB1*07 allele was higher in the CSS patients than in controls (27.1% versus 13.3%; chi(2) = 12.64, P = 0.0003, corrected P [P(corr)] = 0.0042, odds ratio [OR] 2.42, 95% confidence interval [95% CI] 1.47-3.99). The HLA-DRB4 gene, present in subjects carrying either HLA-DRB1*04, HLA-DRB1*07, or HLA-DRB1*09 alleles, was also far more frequent in patients than in controls (38.5% versus 20.1%; chi(2) = 16.46, P = 0.000058, P(corr) = 0.000232, OR 2.49, 95% CI 1.58-3.09). Conversely, the frequency of the HLA-DRB3 gene was lower in patients than in controls (35.4% versus 50.4%; chi(2) = 7.62, P = 0.0057, P(corr) = 0.0228, OR 0.54, 95% CI 0.35-0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA)-positive, with features of small-vessel vasculitis, and ANCA-negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA-DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001). CONCLUSION: These findings indicate that HLA-DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease.     

Associations of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in south India.

SETTING: Tuberculosis is endemic in south India: sputum positive pulmonary tuberculosis is predisposed by HLA-DR2 in south India and few other populations of the world. OBJECTIVE: To study HLA-DRB1, DQB1, DQA1 and DPB1 allelic polymorphism in pulmonary tuberculosis patients and endemic controls from south India. DESIGN: One hundred and twenty-six, sputum positive pulmonary tuberculosis patients and 87, endemic controls, from Madurai were studied for MHC class II allelic polymorphism by PCR-SSOP method. XI IHWC primers and probes and non-radioactive probing methods were employed. RESULTS: HLA DRB1*1501 and DQB1*0601 predisposed for pulmonary tuberculosis (DRB1*1501: odds ratio (OR) = 2.68, 95% confidence interval (CI) = 1.30-5.89, P value (P) = 0.013, aetiological fraction (EF) = 0.17; DQB1*0601: OR = 2.32, CI = 1.29-4.27, P = 0.008, EF = 0.26). Haplotype DRB1*1501-DQB1*0601 was higher in patients (1324 per 10,000, X2 = 27.07) than controls (F = 404/10,000, X2 = 8.84). In a subset of 63 caste matched samples, DPB1*04 was preventive (OR = 0.45, CI = 0.21-0.95, P = 0.036, PF = 0.26): the distributions of DRB1*1501-DQB1*0601-DPB1*04 phenotypes were different between patients and controls (P = 0.0092). These alleles were predominant in patients and controls of T5SU caste. CONCLUSION: HLA-DRB1*1501 and DQB1*0601 predisposed to sputum positive pulmonary tuberculosis, and DPB1*04 was preventive and epistatic to this risk. Caste T5SU is an ideal model to study immunology of tuberculosis.