IL-1B基因多态性和H.pylori感染与汉族人胃癌的相关性研究

目的：通过比较胃癌患者与匹配人群的幽门螺旋杆菌（Helicobacter pylori，H.pylori）感染率和IL-1B基因多态性，探讨IL-1B基因多态性是否增加H．pylori感染后胃癌发生的危险性。方法：采用聚合酶链反应-限制性片段长度多态性（Restriction fragment length polymorphism，RFLP）分析法检测胃癌低发区84例胃癌患者和84例与之性别、年龄匹配的普通人群的1L-1B基因多态性。采用酶联免疫吸附法（Enzyme—linked immunosorbent assay，ELISA）检测上述人群中的H.pylori感染率。结果：①胃癌患者IL-1B-511T／T基因型频率显著高于性别、年龄匹配的对照人群（P〈0．05），IL-1B-31T／T基因型频率在两组间无显著差异（P〉0．05）。84例胃癌患者的H.pylori感染率显著高于对照人群（P〈0．01）。胃癌患者H.pylori阳性感染者IL-1B-511 T／T基因型个体显著多于对照人群。结论：H.pylori感染者胃癌组织中IL-1B-511 T／T基因型为主，提示IL-1B-511 T／T基因型可能增加H.pylori感染后中国汉族人群发生胃癌的危险性，而IL-1B-31基因型与H.pylori感染后中国汉族人群胃癌发生无显著相关性。     

1526名广州市公务员体检糖尿病视网膜病变的现况

目的对体检公务员患糖尿病视网膜病变的情况进行分析,为临床防治提供依据。方法以2012年1-6月在广东省人民医院进行体检的1526名公务员为研究对象,调查内容包括基本情况、相关病史资料、相关实验室检查,并进行常规眼科检查等。结果研究对象的糖尿病患病率为15.66%（239/1526）,并发糖尿病视网膜病变的患病率为32.64%（78/239）。糖尿病视网膜病变的患病率在不同性别和不同年龄段之间差异无统计学意义（P〉0.05）。糖尿病视网膜病变组与非糖尿病视网膜病变的糖尿病组的身高、体重、空腹血糖、糖化血红蛋白、甘油三脂、高密度脂蛋白、低密度脂蛋白比较差异无统计学意义（P〉0.05）,而两组间的病程、收缩压、舒张压、餐后2h血糖、总胆固醇、血肌酐、尿素氮比较差异具有统计学意义（P〈0.05）。结论该研究人群糖尿病视网膜病变患病率高,糖尿病视网膜病变患者同时患高血压、高胆固醇、肾功能异常等全身异常的几率大。     

HLA-DQA1基因多态性与HBV感染结局相关

目的探讨中国汉族人群人类白细胞抗原(HLA)-DQA1基因多态性是否与乙型肝炎病毒(HBV)感染结局相关联。方法以213例HBV自限性感染者和420例慢性乙肝患者为研究对象,应用聚合酶链反应-序列特异性引物(PCR-SSP)技术进行HLA-DQA1基因分型,用EPI和SPSS软件分析DQA1多态性的分布频率及其组间差异。结果DQA1*0102在慢性乙肝组的分布频率显著低于HBV自限性感染组(15.47%比较20.42%,P<0.05),而DQA1*0201在慢性乙肝组的分布频率显著高于HBV自限性感染组(10.48%比较6.10%,P<0.05)。调整性别、年龄等混杂因素影响的非条件logistic回归分析结果显示,与HLA-DQA1其他等位基因相比,携带DQA1*0102者降低慢性乙肝发生的风险(P<0.05,OR=0.69,95%C I:0.49-0.96),而携带DQA1*0201者增加慢性乙肝发生的风险(P<0.05,OR=1.77,95%C I:1.09-2.87)。结论HLA-DQA1基因多态性可能是影响HBV感染结局的重要宿主遗传因素。     

Non-proliferative diabetic retinopathy symptoms detection and classification using neural network

Diabetic retinopathy (DR) causes blindness in the working age for people with diabetes in most countries. The increasing number of people with diabetes worldwide suggests that DR will continue to be major contributors to vision loss. Early detection of retinopathy progress in individuals with diabetes is critical for preventing visual loss. Non-proliferative DR (NPDR) is an early stage of DR. Moreover, NPDR can be classified into mild, moderate and severe. This paper proposes a novel morphology-based algorithm for detecting retinal lesions and classifying each case. First, the proposed algorithm detects the three DR lesions, namely haemorrhages, microaneurysms and exudates. Second, we defined and extracted a set of features from detected lesions. The set of selected feature emulates what physicians looked for in classifying NPDR case. Finally, we designed an artificial neural network (ANN) classifier with three layers to classify NPDR to normal, mild, moderate and severe. Bayesian regularisation and resilient backpropagation algorithms are used to train ANN. The accuracy for the proposed classifiers based on Bayesian regularisation and resilient backpropagation algorithms are 96.6 and 89.9, respectively. The obtained results are compared with results of the recent published classifier. Our proposed classifier outperforms the best in terms of sensitivity and specificity.     

锰超氧化物歧化酶基因Ala(-9)Val多态性与2型糖尿病视网膜病变的相关性

目的 探讨锰超氧化物歧化酶(manganese superoxide dismutase,Mn-SOD)基因Ala(-9)Val多态性与2型糖尿病视网膜病变发生的关联性.方法 应用PCR-直接测序方法检测了中国湖北地区汉族264例2型糖尿病患者和198名正常对照者的Mn-SOD基因Ala(-9)Val多态性(GCT→GTT).结果 (1)2型糖尿病组与正常对照组比较,VV基因型频率(72.7%vs 67.2%,P>0.05)与V等位基因频率(76.1%vs71.0%,P>0.05)差异无统计学意义.(2)在2型糖尿病者中,有糖尿病视网膜病变(diabetic retinopathy,DR)组 VV基因型频率为79.2%,与无糖尿病视网膜病变(non-diabetic retinopathy,NDR)组(66.9%)比较,差异有统计学意义(x2=5.015,P=0.025);V等位基因频率在DR组为82.4%,NDR组为70.5%,差异亦有统计学意义(x2=10.253,P=0.001);NDR组与正常对照组比较,VV基因型频率(66.9%vs67.2%,P>0.05)及V等位基因频率(70.5%vs 71.0%,P>0.05)差异无统计学意义,V等位基因与2型糖尿病视网膜病发生相关(OR=1.96,95%CI:1.29-2.97).(3)基因型为VV型的2型糖尿病患者其Nn-SOD水平较AA型、AV型患者低,差异有统计学意义(P=0.025),其总超氧化物歧化酶有增加趋势,但差异无统计学意义(P>0.05).结论 Mn-SOD基因Ala(-9)Val多态性与2型糖尿病发病无关,但可能参与了2型糖尿病视网膜病变的发生、发展过程.     

Association between interleukin-18 gene polymorphism 105A/C and asthma

BACKGROUND: IL-18 has been shown to exert anti-allergic or allergy-promoting activities, but the existence of genetic polymorphisms in the coding regions of IL-18 gene has not been demonstrated. OBJECTIVE: The aim of this study was to investigate whether polymorphism is present in the coding regions of the IL-18 gene and, if so, to further analyse the association between polymorphism and asthma in a case-control study. METHODS: We screened the coding regions of the IL-18 gene for polymorphisms by using PCRsingle-stranded conformation polymorphism and direct sequencing of PCR products, followed by analysis of the association between polymorphism and asthma. RESULTS: We identified one polymorphism (105A/C) in the coding regions. The frequency of the 105A allele was significantly higher in asthmatic patients than in controls (P<0.01; odds ratio (OR)=1.83 (1.37-2.26)). Significant linkage disequilibrium was observed between the 105A/C and -137G/C polymorphisms in the 5' flanking region of the IL-18 gene (D=0.58, P<0.0001). However, in asthmatic patients the 105A allele was not associated with either total serum IgE or IL-18 levels. CONCLUSION: The 105A/C polymorphism of the IL-18 gene may be associated with the pathogenesis of asthma.     

Association of interleukin-1beta and interleukin-1 receptor antagonist polymorphisms with bacterial vaginosis in non-pregnant Italian women

Bacterial vaginosis (BV) is the most prevalent alteration of vaginal microflora worldwide. BV is a polymicrobial disorder, and its etiology is elusive. Factors predisposing to this recurrent condition are not fully characterized. We aimed to investigate whether interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) polymorphisms are associated with BV in non-pregnant white Italian women. Genomic DNA was obtained from 164 BV positive, and 406 control women. Two diallelic polymorphisms in the IL-1beta gene (IL-1B) representing C/T base transitions at - 511 and + 3954 positions and a variable number tandem repeats (VNTR) in intron 2 of the IL-1ra gene (IL-1RN) were assessed. We demonstrated that women who were homozygous for - 511 CC or + 3954 TT of the IL-1B gene were at increased risk for BV with an odds ratio (OR) = 1.5 [95% confidence interval (CI) = 1.03-2.14, P = 0.032], and OR = 2.8 (95% CI = 1.37-5.88, P = 0.004), respectively. The haplotype - 511/ + 3954 T-C was protective for BV, with an OR = 0.7 (95% CI = 0.49-0.90, P = 0.009). The IL-1RN VNTR genotype was not associated with BV, although the rare allele 3 showed a trend towards protection (P = 0.049). These data show that host genetic variants at the IL-1beta locus predispose to BV among Caucasian non-pregnant women. Further studies will determine whether these genetic polymorphisms modulate the risk for BV recurrence, and/or BV associated severe adverse outcomes as preterm birth and human immunodeficiency virus transmission.     

糖尿病视网膜病MTHFR基因多态性及其与血浆同型半胱氨酸水平的关系

目的：研究亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）基因多态性及血浆同型半胱氨酸水平与2型糖尿病视网膜病的关系。方法：应用聚合酶链反应－限制性内切酶片段长度多态性技术检测208例2型糖尿病患者（其中110例伴视网膜病）及57名正常对照的MTHFR C677T基因型，采用高效液相色谱法测定血浆同型半胱氨酸水平。结果：糖尿病视网膜病组MTHFR基因TT纯合基因型、CT杂合基因型及T等位基因频率（分别为28．18％、41．82％、49．09％）均明显高于糖尿病不伴视网膜病组（分别为18．37％、29．59％、33．16％）及正常对照组（分别为17．54％、28．07％、31．58％），基因型和等位基因频率分布差异均有显著性（P＜0．01），而MTHFR基因多态性在糖尿病不伴视网膜病组与正常对照组之间差异无显著性（P＞0．05），T等位基因与糖尿病视网膜病的发生密切相关（OR＝1．94，95％CI；1．31－2．88）。糖尿病视网膜病组、糖尿病不伴视网膜病组及正常对照组中，MTHFR基因有C677T突变者血浆同型半胱氨酸水平均显著高于无基因突变者。结论：MTHFR基因C677T位碱基突变致血浆同型半胱氨酸水平升高可能是糖尿病视网膜病发病的重要遗传因素。     

白介素受体相关激酶-1基因多态性与类风湿关节炎的相关性

目的探讨白介素受体相关激酶-1(IRAK1)rs3027898和rs1059703多态性性与类风湿关节炎(RA)易感性及临床参数的关系。方法收集RA患者123例和体检的220名健康对照者外周血标本,采用聚合酶链反应-连接酶检测反应(PCR-LDR)方法检测IRAK1 rs3027898和rs1059703基因多态性,收集并计算RA患者临床参数:发病年龄、性别、RF抗体、抗CCP抗体、RA疾病活动(DAS28≥3.2)、骨破坏和用药情况。结果 RA组IRAK1 rs3027898和rs1059703的基因型频率和等位基因频率与健康对照组比较,差异无统计学意义(P>0.05)。RA患者IRAK1 rs3027898和rs1059703基因型与发病年龄、性别、RF抗体和抗CCP抗体阳性率、骨破坏阳性率均无相关性(P>0.05)。RA患者IRAK1 rs3027898基因型与RA疾病活动无相关性(P>0.05),RA患者IRAK1 rs1059703基因型与RA疾病活动存在相关性(P<0.05),携带CT+TT基因型RA患者疾病活动的风险是携带CC基因型RA患者4.243倍(P=0.023,OR=4.243,95%CI为1.223～14.715)。结论我国汉族人群中,IRAK1 rs3027898和rs1059703多态性与RA的易感性无关,但IRAK1 rs1059703多态性可能是RA患者疾病活动的一个遗传危险因素。     

糖尿病视网膜病变图像数据库建立及应用

目的评价基于糖尿病视网膜病变(DR)图像数据库的临床应用技术,探讨其在临床DR早期诊断中的作用。方法采集1100例DR患者的眼底图像,经过初选和归纳分析后选择300只眼,建立微型DR图像数据库及应用软件技术。对100例糖尿病患者的眼底照相和荧光素眼底血管造影(FFA)检查图像进行人工直接诊断,并进行基于DR图像数据库技术的虚拟FFA诊断,对两者各层诊断符合情况进行统计分析,确定其诊断一致性。结果在DR患者不同分期的层次中,FFA检查诊断相符程度均大于80%,人工直接诊断和虚拟FFA诊断的总符合率为90%。结论虚拟FFA诊断与DR眼底照相诊断有较高的一致性,该图像数据库的建立和应用技术可指导和规范临床DR的早期诊疗,也为有创性FFA检查在DR诊治中合理应用提供依据和参考。     

Involvement of RhoA/ROCK1 signaling pathway in hyperglycemia-induced microvascular endothelial dysfunction in diabetic retinopathy

Diabetic retinopathy (DR) is a well-known serious complication of diabetes mellitus (DM), and can eventually advance to end-stage blindness. In the early stage of DR, endothelial cell barrier disorganized primarily and tight junction (TJ) protein composition transformed subsequently. The small GTPase RhoA and its downstream effector Rho-associated coiled-coil containing protein kinase 1 (ROCK1) regulate a mass of cellular processes, including cell adherence, proliferation, permeability and apoptosis. Although RhoA inhibitors have provided substantial clinical benefit as hypertonicity therapeutics, their use is limited by complex microenvironment as DR. While ample evidence indicates that TJ can be influenced by the RhoA/ROCK1 signaling, the underlying mechanisms remain incompletely understood. Here, we have uncovered a significant signaling network involved in diabetic retinal microvascular endothelial dysfunction (RMVED). Our results indicated that the activation of RhoA/ROCK1 pathway due to high glucose played a key role in microvascular endothelial cell dysfunction (MVED) by way of directly inducing TJ proteins over-expression during DR. We demonstrated that inhibition of RhoA/ROCK1 may attenuate the hypertonicity of endothelial cell caused by high glucose microenvironment meanwhile. Besides, chemical and pharmacological inhibitors of RhoA/ROCK1 pathway may partly block inflammation due to DR. Simultaneously, the apoptosis aroused by high glucose was also prevented considerably by fasudil, a kind of pharmacological inhibitor of RhoA/ROCK1 pathway. These findings indicate that RhoA/ROCK1 signaling directly modulates MVED, suggesting a novel therapeutic target for DR.     

Interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms are not associated with tubal pathology and Chlamydia trachomatis-related tubal factor subfertility

BACKGROUND: Chlamydia trachomatis infections have been associated with tubal pathology. However, not all C.trachomatis-infected women actually develop tubal pathology. Recently, host genetic factors such as the interleukin-1 gene cluster have been linked to inflammatory and infectious diseases. METHODS: Dutch Caucasian women were investigated for (i) the role of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms in tubal pathology (group 1); and (ii) the presence of these gene polymorphisms in C.trachomatis IgG-positive women with and without tubal pathology (group 2). Group 1 consisted of women with (n = 40) or without (n = 95) tubal pathology, respectively, and group 2 of C.trachomatis IgG-positive women of whom 28 had tubal pathology at laparoscopy and 47 did not. IL-1B-511 and IL-1B+3954 gene polymorphisms were assessed by PCR-restriction fragment length polymorphism (RFLP), and the variable number of tandem repeats (VNTR) of the IL-1RN gene were assessed by a PCR-based assay. RESULTS: Neither IL-1B-511, IL-1B+3954 nor IL-1RN genotypes, allele or carrier frequencies showed significant association with tubal pathology or C.trachomatis post-infection-based tubal pathology. CONCLUSIONS: The data obtained suggest that specific IL-1 gene polymorphisms are not associated with the tubal pathology risk or to the development of C.trachomatis-based post-infectious severe sequelae.     

CYP1B1基因多态性与子宫内膜异位症易感性的相关研究

目的 研究CYP1B1基因第2外显子119(G-T)、第3外显子432(C-G)多态性与子宫内膜异位症(endometriosis,Ems)易感性的关系.方法 采用等位基因特异性聚合酶链反应对55例Ems患者和45例对照组进行CYP1B1基因第2外显子119(G-T)、第3外显子432(C-G)突变分析,探讨Ems的发生与CYP1B1基因多态性之间的相关性.结果 CYP1B1基因密码子119中等位基因G、T在Ems组和对照组分布的差异有统计学意义(P＜0.05),其中等位基因T使Ems发病风险提高2.061倍;CYP1B1基因密码子119G/T各基因型分布两组间差异有统计学意义(P＜0.05),纯合突变(T/T)基因型、杂合突变(G/T)基因型与野生型(G/G)基因型相比,患Ems的危险度分别为2.625倍和3.214倍.以CYP1B1联合野生型GG和CC个体的OR值为1相比,CYP1B基因密码子119杂合型突变(Ala/Ser)合并密码子432野生型个体的OR值为2.976,95%CI:1.129～7.848,P＜0.05.结论 CYP1B1基因第2外显子119(G-T)突变等位基因与Ems的发生有一定关系,突变基因型增加了Ems的发病风险;CYP1B1基因第2外显子杂合型突变(Ala/Ser)联合密码子432野生型能增加Ems的发病风险.     

Impact of IL28B gene polymorphisms rs8099917 and rs12980275 on response to pegylated interferon-α/ribavirin therapy in chronic hepatitis C genotype 4 patients

Host genetic factors may predict the outcome and treatment response in hepatitis C virus (HCV) infection. One of these factors is the single nucleotide polymorphisms of the interleukin 28B (IL28B) gene. We sought to evaluate the outcome of pegylated interferon and ribavirin therapy in association with IL-28B rs8099917 and rs12980275 in patients infected with HCV genotype 4. A total of 180 patients with chronic hepatitis C were selected from Egyptians who have received combined therapy with pegylated interferon and ribavirin for 6 months and their response was evaluated after follow-up at 0, 6, 12, 24 and 48 weeks from the beginning of the therapy. Blood samples were collected from responders and non-responders. Genomic DNA was extracted from whole blood and genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Our results showed that TT genotype of rs8099917 was associated with higher sustained viral response (SVR) rates and G allele represented a risk factor for failure of response (OR = 3.7, CI = 1.8:7.64) while rs12980275 was not significantly associated with SVR in genotype 4 Egyptian patients. The determination of IL-28B SNPs may be useful in enhancing correct prediction of SVR achievement in treating this group of genotype 4 patients.     

Association of HSPA1B SNP rs6457452 with Alopecia Areata in the Korean Population

The heat shock 70?kDa protein 1B (HSPA1B), which has been well-studied among the famous heat shock proteins HSPA1A/B/L, is related to autoimmune diseases, including Alopecia Areata (AA). In this study, the association of a 5’-untranslated region (5’UTR) SNP rs6457452 and a promoter SNP rs2763979 (‐1140C?>?T) of HSPA1B with AA was investigated in 236 controls and 228 AA patients. Statistical analyses using the multiple logistic models were done, according to the onset and the clinical features of AA, including the age of onset, family history, type of AA lesion, nail involvement and body hair involvement. The results showed that rs6457452 was associated with the onset of AA (p?<?0.002). In the analysis of clinical features of AA, rs6457452 was weakly related to the age of onset (p?≤?0.04) and that rs2763979 was only weakly related to the type of AA lesion (p?=?0.041). In conclusion, we suggest that the 5’UTR SNP rs6457452 of HSPA1B may be associated with the onset of AA and the T allele of rs6457452 may confer the reduced susceptibility to AA in the Korean population.     

难治性癫痫患病风险与MDR1基因tag SNPs rs3789243及rs2235046位点多态性的相关性

目的探讨MDR1基因tag SNPs与中国汉族难治性癫痫患病风险的关系。方法安徽合肥周边地区的汉族癫痫患者164例和健康对照198例,通过传统SNP基因分型技术PCR-CTPP对MDR1基因的标签SNPs rs3789243和rs2235046进行基因分型,随机样本测序验证,并进行统计学分析。结果 SNPs rs3789243的CC基因型分布频率在癫痫病例组和正常对照组之间、难治组和对照组之间均有显著性差异(P<0.01),相对危险度分别为4.315和7.123(P<0.01);SNPs rs2235046的AA基因型分布频率在癫痫病例组和对照组之间有显著性差异(P<0.01),相对危险度为2.837(P<0.01)。结论 MDR1基因多态性rs3789243基因型CC和rs2235046基因型AA可能与癫痫的患病风险升高有关;rs3789243基因型CC可能与IE风险升高有关。     

Association between HSD17B1 rs605059 polymorphisms and the risk of uterine diseases: a systemic review and meta-analysis

The aim of this study was to evaluate the HSD17B1 gene polymorphisms in the risks of endometrial cancer, endometriosis and uterine leiomyoma by meta-analysis. A comprehensive electronic search was conducted in PubMed, Medline (Ovid), Embase, Weipu, Wanfang and CNKI. The pooled ORs were performed using the Revman 5.2 softerware. 8 case-control studies were included: 3 were about endometrial cancer, 4 were about endometriosis and 1 was about uterine leiomyoma. The result showed no significant association between HSD17B1 rs605059 gene polymorphisms and risks of endometrial cancer (AA vs. AG+GG: OR = 1.11, 95% CI = 0.94-1.32; AA+AG vs. GG: OR = 1.79, 95% CI = 0.42-7.52; AG vs. AA+ GG: OR = 0.87, 95% CI = 0.76-1.00; AA vs. GG: OR = 1.43, 95% CI = 0.62-3.30; A vs. G: OR = 1.00, 95% CI = 0.91-1.11) or endometriosis (AA vs. AG+GG: OR = 0.99, 95% CI = 0.75-1.32; AA+AG vs. GG: OR = 1.73, 95% CI = 0.92-3.25; AG vs. AA+ GG: OR = 1.24, 95% CI = 1.00-1.53; AA vs. GG: OR = 1.54, 95% CI = 0.79-2.97; A vs. G: OR = 1.23, 95% CI = 0.90-1.68). No association was found in a subgroup analysis based on Asian ethnicity for endometriosis. This meta-analysis suggested that HSD17B1 rs605059 polymorphisms were not associated with the risks of endometrial cancer and endometriosis. Further studies are needed to validate the conclusion and clarify the relationship between HSD17B1 rs605059 polymorphisms and the risk of uterine leiomyoma.     

糖尿病视网膜病变相关基因多态性的研究进展

糖尿病视网膜病变是目前国际上最主要的致盲性眼病之一,患病率日渐升高.其发生和发展与血糖水平、糖尿病病程、环境及遗传等多种因素有关.近些年来,随着基因多态性与糖尿病视网膜病变关系的研究不断深入和进展,已经筛选出了可能与之相关的数十 种基因,其中几种基因多态性已经被证实为糖尿病视网膜病变发生的独立危险因素.现将与糖尿病视网膜病变密切相关的基因多态性研究进展作一综述.     

Interaction analysis between BLK rs13277113 polymorphism and BANK1 rs3733197 polymorphism,MMEL1/TNFRSF14 rs3890745 polymorphism in determining susceptibility to rheumatoid arthritis

Two pairwise genetic interactions (B cell lymphocyte kinase (BLK) rs13277113,B cell scaffold protein with ankyrin repeats 1 (BANK1) rs3733197and BLK rs13277113 membrane metalloendopeptidase like 1 (MMEL1)/ tumor necrosis factor receptor superfamily member 14 (TNFRSF14) rs3890745) have been demonstrated in determining susceptibility to rheumatoid arthritis (RA) without replication, thus this study was performed to examine whether abovementioned genetic polymorphisms were associated with RA and further tests were performed to see whether aforementioned genetic interactions existed in RA among Chinese population. A total of 328 patients with RA and 449 healthy control subjects were included in the current study. The polymorphisms were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. The association of RA with each polymorphism was analyzed by multivariate logistic regression model. Interaction analysis was done by multiple methods. Significant difference in genotype distribution of BLK rs13277113 polymorphism between RA patients and healthy controls was found (p?=?1.01?×?10^?2). The major allele A of BLK rs13277113 polymorphism was significantly increased in RA patients compared with controls (OR?=?1.36, 95% CI?=?1.08–1.71, p?=?9.27?×?10^?3). Significant association of RA with the major allele A of BLK rs13277113 polymorphism under dominant model was also detected (OR?=?2.74, 95% CI?=?1.42–5.29, p?=?2.73?×?10^?3). However, we did not find significant association between neither BANK1 rs3733197 polymorphism nor MMEL1/TNFRSF14 rs3890745 polymorphism and RA. Non-significant evidence was found for neither additive nor multiplicative interaction for these two pairwise genetic polymorphisms (BLK rs13277113-BANK1 rs3733197; BLK rs13277113-MMEL1/TNFRSF14 rs3890745). Significant association of RA with G allele of BANK1 rs3733197 polymorphism was only found among individuals carrying A/A genotype of the BLK rs13277113 polymorphism (OR?=?1.49, 95% CI?=?1.01–2.18, p?=?.04). In summary, our results indicated that the BLK rs13277113 polymorphism was involved in the genetic background of RA in Chinese population and the association of BANK1 rs3733197 polymorphism with RA was dependent on the genotype of BLK rs13277113 polymorphism, highlighting B-cell response implicated in the pathogenesis of RA.     

HLA-DQA1基因多态性和HBV感染结局的关联

目的 探讨人类白细胞抗原(HLA)DQA1基因多态性与乙型肝炎病毒(HBV)感染临床结局的关联.方法 临床收集慢性乙型肝炎(120例)、慢性HBV携带者(60例)、自限性HBV感染者(60例)三组病例,前两组诊断均经肝活检证实.聚合酶链反应序列特异性引物(PCR-SSP)法检测HLA-DQA1基因型,比较组间基因频率的差异.结果 (1)HLA-DQA1*0201在慢性乙型肝炎组的分布频率显著高于自限性HBV感染组(38.3% vs 5.8%,P<0.001,A=10.04,95% CI:4.48～22.48);HLA-DQA1*0102的分布频率显著低于自限性HBV感染组(9.6% vs 36.7%,P<0.001,A=0.183,95%CI:0.10～0.32).(2)HLA-DQA1*0201在慢性乙型肝炎组的分布频率显著高于慢性HBV携带者组(38.3% vs 7.5%,P<0.01,A=7.667,95% CI:3.7～15.87);HLA-DQA1*0102的分布频率显著低于慢性HBV携带者(20% vs 9.6%.P<0.01,A=0.424,95% CI:0.23～0.79).结论 HLA-DQAI基因多态性影响HBV感染临床结局,其中DQA1*0102呈保护作用,DQA1*0201可能促进HBV感染的慢性化和肝炎的发生.