Associations between polymorphisms in IL-12A, IL-12B, IL-12Rβ1, IL-27 gene and serum levels of IL-12p40, IL-27p28 with esophageal cancer

Purpose

The aim of this study was to investigate whether IL-12A, IL-12B, IL-12Rβ1, and IL-27 gene polymorphisms and serum levels of IL-12, IL-27 are associated with esophageal cancer.

Methods

We genotyped IL-12A gene rs568408, IL-12B gene rs3212227, IL-12Rβ1 gene 378 C/G, IL-27 gene rs153109, rs17855750, and rs181206 polymorphisms in a case–control study of 426 esophageal cancer patients and 432 health controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay.

Results

Both serum IL-12p40 and IL-27p28 levels were significantly higher in controls than those in patients (P?<?0.01). Rs568408 AG/AA, rs3212227 CC/AC, and IL-12Rβ1 378 GG/GC genotypes were associated with significantly increased risk of esophageal cancer (rs568408: χ²?=?5.704, P?=?0.017; rs3212227: χ²?=?7.689, P?=?0.006; IL-12Rβ1 378C/G: χ²?=?5.206, P?=?0.023). Moreover, rs3212227 CC/AC and 378 GG/GC genotypes were observed significantly associated with decreased serum IL-12p40 level in patients compare to other genotypes (rs3212227: t?=?2.129, P?=?0.034; IL-12Rβ1 378 C/G: t?=?2.178, P?=?0.030). Furthermore, frequency of rs3212227 CC/AC genotypes was significantly higher in patients with poor differentiation than those with AA genotype (χ²?=?4.314, P?=?0.035).

Conclusion

Our data suggest that the impaired production of IL-12p40 and IL-27p28 behaves as risk factors for esophageal cancer occurrence. IL-12B gene rs3212227 CC/AC and IL-12Rβ1 gene 378 GG/GC genotypes, which associated with decreased IL-12p40 level, may contribute to esophageal cancer susceptibility.     

白细胞介素-12p403'非翻译区基因多态性与丙型肝炎病毒感染的相关性

目的 探讨丙型肝炎患者IL-12p40 3'非翻译区rs3212227位点基因多态性与HCV感染的关系.方法 应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)和DNA测序的方法榆测127例丙型肝炎患者IL-12 p40 3'非翻译区rs3212227位点的基因型,采用荧光定量PCR技术测定丙型肝炎患者血清HCV RNA水平.组间基因型及等位基因分布频率比较采用χ2检验.结果 丙型肝炎患者IL-12 p40 3'非翻译区rs3212227位点AA、AC、CC基因型分布频率分别为34.6%、40.9%和24.4%.等位基因A、C分布频率分别为55.1%、44.9%.丙型肝炎患者中HCVRNA≥2.0×106拷贝/mL组IL-12 p40 rs3212227位点C等位基因携带者分布频率明显高于HCVRNA<2.0×106拷贝/mL组(χ2=7.367,P=0.007).IFN无应答组IL-12 p40 rs3212227位点C等位基因分布频率明显高于IFN应答组(χ2=4.942,P=0.026).结论 IL-12p40 3'非翻译区rs3212227位点基因多态性与HCV感染具有相关性,携带C等位基因的个体可能更利于HCV复制,而不利于IFN治疗.

Abstract：

Objective To investigate the association between single nucleotide polymorphism (SNP) of interleukin-12 (IL-12) p40 3'untranslated region rs3212227 site and hepatitis C virus (HCV) infection. Methods Patients with hepatitis C (n=127) were genotyped and analyzed for the SNP of IL-12 p40 rs3212227 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The serum HCV RNA levels of patients with hepatitis C were detected using real time fluorescence quantitative-polymerase chain reaction (FQPCR). Inter-group comparisons of genotype and allele frequency were analyzed using chi-square test.Results In patients with hepatitis C, the frequencies of AA, AC and CC genotypes of IL-12 p40 rs3212227 site were 34. 6% ,40. 9% and 24. 4% , respectively,and the frequencies of allele A, C of IL12 p40 rs3212227 site were 55.1% and 44. 9%, respectively. The frequency of rs3212227 C allele in patients with HCV RNA ≥2. 0× 106 copy/mL was higher than that in patients with HCV RNA <2. 0 ×106 copy/mL (χ2 =7. 367, P = 0. 007). The frequency of rs3212227 C allele in responders to interferon (IFN) therapy was lower than that in patients with nonresponse to IFN therapy (χ2 =4. 942,P=0. 026). Conclusions The SNP of rs3212227 is correlated with HCV infection. The carriers with C allele may be susceptible to HCV infection, while resistant to IFN therapy.     

Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection

AIM:To identify the relationship between the tagging single nucleotide polymorphism sites(tagSNPs)of the Interleukin-18(IL-18)gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients.METHODS:Five hundred and one cases of chronic hep-atitis B virus(HBV)infection and 301 HBV natural clearance controls were studied.Two tagSNPs in the IL-18 gene(rs1946518A/C and rs574424C/G)were genotyped by the Multiplex Snapshot technique.The genotype and allele frequencies were calculated and analyzed.RESULTS:In the genotypes of rs1946518,the AA type was present at a higher frequency in the patients compared to those in the controls.Odds ratio(OR)of theAA genotype for the comparison with that of the AC and the CC genotype was 1.537(95%confidence intervals(CI):1.116-2.218,P=0.009<0.025).In pheno-types,the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls(P=0.017<0.025).OR of the allele A for the comparison with that of the allele C was 1.279(95%CI:1.045-1.567).As for the rs574424 genotypes,no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed.No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed.CONCLUSION:The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene.However,no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.     

Polymorphisms of micro RNA target genes IL12B,INSR, CCND1 and IL10 in gastric cancer

AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and Latvia.Controls were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy.Gastric cancer(GC)patients had histopathological verification of gastric adenocarcinoma.Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells.IL12B TG(rs1368439),INSR TC(rs1051690),CCND1 AC(rs7177)and IL10 TC(rs3024498)SNPs were genotyped by the real-time polymerase chain reaction.Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of birth.RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690.The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,P0.021).Logistic regression analysis revealed that only one polymorphism(rs1051690 in INSR gene)was associated with increased risk of GC.Carriers of CT genotype had higher odds of GC when compared to CC genotype(OR=1.45,95%PI:1.08-1.95,P=0.01).Similar association was observed in a dominant model for INSR gene,where comparison of TT+CT vs CC genotypes showed an increased risk of GC(OR=1.44,95%PI:1.08-1.90,P=0.01).Other analyzed SNPs were not associated with the presence of GC.CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC,while polymorphisms in IL12B,CCND1 and IL10genes are not linked with the presence of GC.     

Distribution of IL28B Genotypes in Iranian Patients with Chronic Hepatitis C and Healthy Individuals

Background

IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon.

Objectives

The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C.

Patients and Methods

In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46).

Conclusions

It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.     

Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma

We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m(2), women with BMI more than or equal to 25 kg/m(2) had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 P(forinteraction) = .034) and IL7R (rs1494555 P(forinteraction) = .016) for NHL overall; IL7R (rs1494555 P(forinteraction) = .016) and TNF (1799724 P(forinteraction) = .031) for B-cell lymphoma; and IL5 (rs2069812 P(forinteraction) = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 P(forinteraction) = .006), IL13 (rs20541 P(forinteraction) = .019), and IL7R (rs1494555 P(forinteraction) = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 P(forinteraction) = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 P(forinteraction) = .013) and TNF (1799724 P(forinteraction) = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.     

血管紧张素原基因启动子区域单核苷酸多态与高血压并发冠心病的关系

目的　研究在中国南方汉人群中 ,血管紧张素原基因 (angiotensinogen ,AGT)启动子区域 2 17位和 2 0位上的二种单核苷酸多态与高血压病 (EH)并发冠心病的关系。方法　运用多重SNaPshot反应 ,对 2 0 5例EH并发冠心病患者、185例EH患者和 185名健康对照者进行G 2 17A和A 2 0C多态基因分型。结果　G 2 17A多态的基因型分布在EH并发冠心病组 (AA =8、AG =71、GG =12 6 )和对照组 (AA =8、AG =37、GG =14 0 )之间有显著性差异 (P =0 0 0 5 ) ;A、G等位基因频率与对照组相比亦有显著性差异 (A 2 1 2 2 %、G 78 78%比A 14 32 %、G 85 6 8% ,P =0 0 12 ) ;A 2 0C多态的基因型分布 (CC、AC、AA)及C、A等位基因频率在二组间的差异无显著性 (分别为CC =5、AC =4 9、AA =15 1比CC =2、AC =6 1、AA =12 2 ,P =0 0 97;C 14 39%、A 85 6 1%比C 17 5 7%、A 82 4 3% ,P=0 2 2 6 )。在男性EH并发冠心病组中 ,G 2 17A和A 2 0C多态的基因型分布及其等位基因频率与对照组相比均有显著性差异 (G 2 17A :AA =7、AG =5 3、GG =86比AA =6、AG =2 8、GG =97,P =0 0 2 2 ;A 2 2 95 %、G 77 0 5 %比A 15 2 7%、G 84 73% ,P =0 0 2 2。A 2 0C :CC =3、CA =2 7、AA =116比CC =2、CA =4 3、AA =86 ,P =0 0 2 3;C 11 30 %     

Factors responsible for the discrepancy between IL28B polymorphism prediction and the viral response to peginterferon plus ribavirin therapy in Japanese chronic hepatitis C patients

Aim: IL28B polymorphisms serve to predict response to pegylated interferon plus ribavirin therapy (PEG IFN/RBV) in Japanese patients with chronic hepatitis C (CHC) very reliably. However, the prediction by the IL28B polymorphism contradicted the virological response to PEG IFN/RBV in some patients. Here, we aimed to investigate the factors responsible for the discrepancy between the IL28B polymorphism prediction and virological responses. Methods: CHC patients with genotype 1b and high viral load were enrolled in this study. In a case-control study, clinical and virological factors were analyzed for 130 patients with rs8099917 TT genotype and 96 patients with rs8099917 TG or GG genotype who were matched according to sex, age, hemoglobin level and platelet count. Results: Higher low-density lipoprotein (LDL) cholesterol, lower γ-glutamyltransferase and the percentage of wild-type phenotype at amino acids 70 and 91 were significantly associated with the rs8099917 TT genotype. Multivariate analysis showed that rs8099917 TG or GG genotype, older age and lower LDL cholesterol were independently associated with the non-virological responder (NVR) phenotype. In patients with rs8099917 TT genotype (predicted as virological responder [VR]), multivariate analysis showed that older age was independently associated with NVR. In patients with rs8099917 TG or GG genotype (predicted as NVR), multivariate analysis showed that younger age was independently associated with VR. Conclusion: Patient age gave rise to the discrepancy between the prediction by IL28B polymorphism and the virological responses, suggesting that patients should be treated at a younger age.     

慢性丙型肝炎患者病毒基因型与IL-28B基因型分布

目的：了解慢性丙型肝炎患者白细胞介素-28B（IL-28B）基因型多态性分布的特点及其临床意义。方法在27例慢性丙型肝炎患者,分离外周血细胞DNA,采用IPLEX Gold法检测宿主IL-28B基因多态性;分析患者IL-28B基因型与血清丙型肝炎病毒（HCV）基因型、HCV RNA载量和肝功能指标的相关性。结果在27例慢性丙型肝炎患者中,感染HCV基因1型1例（3.7%）,1b基因型7例（25.9%）,其它基因型19例（19/27,70.4%）;在IL-28B基因型中,rs12979860 CC基因型、rs12980275 AA基因型及rs8099917 TT基因型共24例（88.9%）,而IL28B rs12979860 CT基因型、rs12980275 GA基因型和rs8099917 GT基因型共3例（11.1%）;在HCV基因1型或1b型感染者中,IL28B rs12979860 CC基因型、rs12980275 AA基因型和rs8099917 TT基因型占62.5%（5/8）,而HCV其他基因型感染者IL28B rs12979860 CC基因型、rs12980275 AA基因型和rs8099917 TT基因型占100%（19/19）;HCV基因1型或1b型感染者与HCV其他基因型感染者比,其IL28B rs12979860位点、rs12980275位点和rs8099917位点基因型分布有显著性差异（P＆lt;0.01）;IL-28B基因多态性分布与患者血清HCV RNA载量或肝功能指标的变化无显著性相关。结论本组慢性丙型肝炎患者HCV基因型大多为非1型;大多数感染者IL-28B基因为rs12979860 CC、rs12980275 AA和rs8099917 TT基因型。     

酒精性肝硬化患者血CTLA-4和PNPLA3基因多态性及其临床意义分析*

目的 探讨细胞毒性T淋巴细胞相关抗原4(CTLA-4)和Patatin样磷脂酶3(PNPLA3)基因多态性与酒精性肝硬化发病的关系。方法 2017年1月～2019年1月我院治疗的酒精性肝硬化患者110例和同期健康人100例,采用聚合酶链反应-限制性片段长度多态性检测血CTLA-4基因rs4675369位点和PNPLA3基因rs738409位点多态性。结果 肝硬化患者CTLA-4基因rs4675369位点为AA型、AG型和GG型比率分别为26.4%、49.1%和24.6%,与健康人的26.0%、50.0%和24.0%比,无显著性差异(P>0.05),等位基因A和G比率分别为50.9%和49.1%,与健康人的51.0%和49.0%比,也无显著性差异(P>0.05);肝硬化患者PNPLA3基因rs738409位点GG基因型和等位基因G比率分别为17.2%和38.2%,显著高于健康人的4.0%和24.0%(P<0.05);血CTLA-4基因rs4675369位点AA型、AG型和GG型和PNPLA3基因rs738409位点CC型、CG型和GG型肝硬化患者血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、谷氨酰转肽酶和碱性磷酸酶水平之间比,差异均无统计学意义(P>0.05)。结论 本研究结果未提示CTLA-4基因多态性与酒精性肝硬化发病存在相关关系,而PNPLA3基因多态性与酒精性肝硬化发病的关系也需要进一步研究明确。     

慢性HBV感染者外周血PNPLA3/PRKAA1基因多态性与肝硬化发生关系研究*

目的 探讨Patatin样磷脂酶域蛋白3(PNPLA3)和腺苷活化蛋白激酶α1亚基(PRKAA1)基因多态性与感染HBV后肝硬化发生的关系。方法 2016年1月～2021年7月我院诊治的乙型肝炎肝硬化患者101例和同期慢性无症状HBV携带者90例,采用聚合酶链反应-限制性片段长度多态性检测血浆PNPLA3基因rs738409、rs139047、rs2294919和PRKAA1基因rs3792822、rs10036575、rs154268位点多态性,应用Logistic回归分析疾病风险关联。结果 肝硬化组PNPLA3基因rs139047位点AA、GA、GA基因型比率分别为18.8%、51.5%和29.7%,与HBV携带者的16.7%、51.1%和32.2%比,无显著性差异(P＞0.05),rs2294919位点CC、TC、TT基因型比率分别为41.6%、45.5%和12.9%,与HBV携带者的38.9%、50.0%和11.1%比,无显著性差异(P＞0.05);PRKAA1基因rs3792822位点GG、GA、AA基因型比率分别为54.5%、38.6%和6.9%,与HBV携带者的55.6%、37.8%和6.7%比,无显著性差异(P＞0.05),rs154268位点CC、CT、TT基因型比率分别为5.0%、35.6%和59.4%,与HBV携带者的4.4%、34.4%和61.1%比,无显著性差异(P＞0.05);肝硬化组PNPLA3基因rs738409位点GG基因型和等位基因G比率分别为19.8%和44.6%,显著高于HBV携带者的8.9%和29.4%(P＜0.05);肝硬化组PRKAA1基因rs10036575位点CC基因型和等位基因C比率分别为38.6%和63.9%,显著高于HBV携带者的23.3%和45.5%(P＜0.05);经非条件Logistic回归模型分析显示PNPLA3基因rs738409位点GG基因型【OR为1.605(95%CI:1.150～2.239)】和PRKAA1基因rs10036575位点CC基因型【OR值为1.507((95%CI:1.097～2.070)】是影响感染HBV后肝硬化发生的危险基因型。结论 感染HBV后发生肝硬化可能与某些特殊基因有关,研究PNPLA3基因和PRKAA1基因可能有助于阐明其中的分子机制。     

Genetic variation in interleukin-28B predicts SVR in hepatitis C genotype 1 Argentine patients treated with PEG IFN and ribavirin

Background and aims. Genetic variations in the interleukin 28B (IL28B) gene have been associated with viral response to PEG-interferon-a/ribavirin (PR) therapy in hepatitis C virus (HCV) genotype 1 infected patients from North America, Europe and Asia. The importance of these IL28B variants for Argentine patients remains unknown.Material and methods. IL28B host genotypes (rs8099917 and rs12979860) were determined in a population of Argentine patients with European ancestry. Results were analyzed looking for their association with sustained virologic response (SVR) to PR therapy and compared with other baseline hosts’ biochemical, histological and virological predictors of response.Results. We studied 102 patients, 60% were men, and 40% of them were rs8099917 TT and 18% rs12979860 CC. Mean baseline serum HCV RNA was 1.673.092 lU/mL and mean F score was: 2.10 ± 1.18 (21% cirrhotic). SVR rate was higher in rs8099917 TT genotypes (55%) when compared to GT/GG (25%) (p = 0.002) and in rs1512979860 CC (64%) than in CT/TT (30%) (p = 0.004). The univariate analysis showed that rs8099917 TT (OR 3.7; 95 %CI 1.5-8.7; p = 0.002), rs12979860 CC (OR 4.6; 95%CI 1.5-13.7; p = 0.006), low viral load (OR 4.6; 95°% CI 1.7-12.6; p = 0.002) and F0-2 (OR 8.5; 95°% CI 2.3-30.6; p = 0.001) were significantly associated with SVR. In the multivariate analysis, rs12979860 CC, rs8099917 TT, viral load < 400.000 IU/mL and F0-2 were associated with SVR rates (p = 0.029, p = 0.012, p = 0.013 and p = 0.004, respectively).Conclusion. IL28B host genotypes should be added to baseline predictors of response to PR therapy in Latin American patients with European ancestry.     

Physical activity modifies the association between CYBA gene polymorphisms and small artery elasticity in a Chinese population

Emerging evidence suggests that increased superoxide production is responsible for a significant proportion of endothelial dysfunction. The relationship between variants of the CYBA gene and cardiovascular diseases is currently debated. In the present study, we investigated the influence of CYBA polymorphisms (rs1049255 and rs7195830) on arterial elasticity in a Chinese population. In the 2178 participants enrolled in the GaoYou study, we measured large artery elasticity (C1) and small artery elasticity (C2) non-invasively, genotyped the CYBA polymorphisms and calculated energy expenditure. The AA genotype of the rs1049255 polymorphism was associated with a lower C2 than were the GG/AG genotypes (5.31±0.11 vs. 5.52±0.06?ml?mm?Hg(-1) × 100; P=0.01). Further analyses revealed an interaction between CYBA polymorphisms and physical activity with respect to C2 (P=0.007 for rs1049255 and P=0.038 for rs7195830). In less physically active participants, the AA genotype of the rs1049255 polymorphism was associated with a significantly lower C2 than the GG/AG genotypes (4.69±0.16 vs. 5.26±0.19?ml?mm?Hg(-1) × 100; P=0.008). In physically active participants, the GG/AG genotypes of rs7195830 polymorphism were correlated with higher C2 values than the AA genotype (5.84±0.08 vs. 5.08±0.32?ml?mm?Hg(-1) × 100; P=0.049). Haplotype analyses revealed higher C2 values in rs1049255G-rs7195830G carriers (P=0.0015). In conclusion, the rs1049255 and rs7195830 polymorphisms of the CYBA gene were associated with C2 in a Chinese population; physical activity could modify this genetic effect.     

Interleukin-21 gene polymorphisms and chronic hepatitis B infection in a Chinese population

AIM: To investigate the relationship between inter-leukin-21(IL21) gene polymorphisms and chronic hepatitis B virus(HBV) infection in a Chinese population. METHODS: In this case-control study, 366 Chinese HBV-infected patients were recruited and divided into hepatocellular carcinoma(HCC; n = 94) and non-HCC(n = 272) groups at The First Affiliated Hospital of Sun Yat-Sen University, from April 2009 to December 2012. In the non-HCC group, the patients were classified into three clinical subsets, 76 patients had chronic hepatitis B, 101 were HBV carriers and 95 patients had HBV-related cirrhosis. Two hundred eight unrelated healthy controls were also included. Genomic DNA was extracted from peripheral blood. Single nucleotide polymorphisms(SNPs) rs13143866, rs2221903, and rs907715 were subsequently genotyped using the SNaP shot SNP technique.RESULTS: There were no significant differences in allele and genotype frequencies of SNPs rs13143866, rs2221903, and rs907715 between chronic HBVinfected patients and control subjects. Furthermore, no significant differences were found in the frequencies of all alleles and genotypes between the HCC group and the non-HCC group. However, in the subgroup analysis, IL21 rs13143866 genotype AA frequency in the HBV carrier group was higher than in controls(OR = 6.280, 95%CI: 1.238-31.854; P = 0.019), and the effect of the recessive model(AA vs GG + GA, OR = 6.505, 95%CI: 1.289-32.828) was observed in the HBV carrier group. IL21 rs2221903 genotype TC frequency in the HBV carrier group was higher than in controls(OR = 1.809, 95%CI: 1.043-3.139; P = 0.035). In the haplotype analysis, the ATA haplotype(rs13143866, rs2221903, and rs907715) of IL21 was more frequent in the HCC group than in the non-HCC group(0.165 vs 0.104, P = 0.044; OR = 1.700, 95%CI: 1.010-2.863).CONCLUSION: Genotypes rs13143866 AA and rs2221903 TC are risk factors for carrying HBV; ATA haplotype increases the risk of HBV-related HCC onsetin a Chinese population.     

DAAM2 polymorphism is closely related to the clinical outcomes of allogeneic hematopoietic stem cell transplantation

Disheveled associated activator of morphogenesis 2 (DAAM2) is one of the key proteins of WNT/plantar cell polarity signaling pathway which is closely linked to oncogenesis, cellular proliferation and regeneration, and stem cell renewal. This study investigated the association of DAAM2 genetic polymorphism with the clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). We selected candidate single nucleotide polymorphisms (SNPs) by DNA chip analysis using Illumina Infinium Human-1 microarrays? on 15 patients who underwent allogeneic HSCT with (N = 7) or without (N = 8) acute graft versus host disease (GvHD). Six SNPs (rs2504787, rs2504086, rs2504082, rs3004067, rs882559, and rs3004070) of DAAM2 were associated with acute GvHD prevalence, and the genotyping was extended to larger population (N = 228). Medical records were reviewed to see the correlation of these SNPs with the clinical outcomes of the patients. In rs2504082 and rs882559, treatment-related mortality was significantly lower in major homozygote than other genotypes (29.3% in AA vs. 44.3% in AG or GG, p = 0.0214; 23.0% in CC vs. 39.9% in CG or GG, p = 0.0072, respectively). Acute GvHD incidence and engraftment time were significantly different according to the specific genotype of selected SNPS in this study. This study is the first report regarding the clinical value of DAAM2 polymorphism as a predictive marker of clinical outcomes of allogeneic HSCT.     

Lack of association of Toll-like receptor 9 polymorphisms with susceptibility to systemic lupus erythematosus in an Asian population: a meta-analysis

Abstract

The association of Toll-like receptor 9 (TLR9) gene polymorphisms with systemic lupus erythematosus (SLE) risk remains controversial and ambiguous. To more precisely estimate the relationship between TLR9 gene polymorphisms and the susceptibility to SLE, a meta-analysis was performed. A total of seven independent studies were involved in this analysis. Meta-analysis was performed for three TLR9 gene polymorphisms (rs187084, rs352139, and rs352140). We have compared allele or genotype frequencies of the polymorphisms in SLE patients and controls. When available studies were pooled into the meta-analysis, there was no evidence showing a significant association between rs187084 and SLE risk in an Asian population (for C vs. T: OR = 0.81, P = 0.117; for CC vs. TT: OR = 0.71, P = 0.158; for CT vs. TT: OR = 0.86, P = 0.085; for CC + CT vs. TT: OR = 0.78, P = 0.093; for CC vs. CT + TT: OR = 0.81, P = 0.285). Similar results were found between rs352139 and SLE. No significant association was detected in any genetic model in the Asian population either (for G vs. A: OR = 1.11, P = 0.095; for GG vs. AA: OR = 1.32, P = 0.238; for GA vs. AA: OR = 1.17, P = 0.084; for GG + GA vs. AA: OR = 1.17, P = 0.073; for GG vs. GA + AA: OR = 1.17, P = 0.404). We found no association between TLR9 gene rs352140 polymorphism and SLE in the Asian population (for A vs. G: OR = 1.02, P = 0.728). In conclusion, there is still not enough evidence to indicate an association between TLR9 gene rs187084, rs352139, and rs352140 polymorphisms and the development of SLE in the Asian population.     

Limited use of interleukin 28B in the setting of response-guided treatment with detailed on-treatment virological monitoring

A single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene is associated with pegylated interferon-alfa-induced viral clearance in hepatitis C virus (HCV) genotype 1 patients. Using a well-characterized cohort of patients randomized to standard versus response-guided therapy, we studied whether the favorable CC type allows shortening of treatment duration. Association with viral kinetics, sustained viral response (SVR), and predictors of response were also analyzed. In the original study, 696 patients were randomized to either standard or variable therapy of 24, 48, or 72 weeks according to first undetectable HCV RNA. Association between IL28B determined by genotyping rs12979860 and end of treatment response and SVR by treatment arm was tested; baseline predictors of response were analyzed using multiple logistic regression. A total of 454 patients were evaluated. The frequency of IL28B type was CC = 29%, CT = 53%, TT = 18%. CC type was strongly associated with rapid virological response (RVR) as well as higher rates of week 8 and week 12 response. CC type was associated with SVR in both arms. In patients with RVR, SVR was high and IL28B type was not associated with SVR. In RVR patients, there was no significant difference in SVR or relapse rates after 24 or 48 weeks by IL28B type. Among non-RVR patients, CC type was associated with SVR at a higher rate than CT/TT, both in standard and variable analysis. However, when week 8 and week 12 responders were considered separately, IL28B type was no longer predictive of SVR. Few CC patients remained viremic beyond week 8 to allow the analysis of relationships between IL28B type and extended treatment. Conclusion: In HCV-1 patients, the favorable CC type strongly predicted higher rates of on-treatment virological milestones and SVR. However, achievement of on-treatment virological milestones was the critical factor in determining outcome. IL28B type appeared to have limited potential for response-guided treatment strategies.     

Lack of association of Toll-like receptor 9 polymorphisms with susceptibility to systemic lupus erythematosus in an Asian population: a meta-analysis

The association of Toll-like receptor 9 (TLR9) gene polymorphisms with systemic lupus erythematosus (SLE) risk remains controversial and ambiguous. To more precisely estimate the relationship between TLR9 gene polymorphisms and the susceptibility to SLE, a meta-analysis was performed. A total of seven independent studies were involved in this analysis. Meta-analysis was performed for three TLR9 gene polymorphisms (rs187084, rs352139, and rs352140). We have compared allele or genotype frequencies of the polymorphisms in SLE patients and controls. When available studies were pooled into the meta-analysis, there was no evidence showing a significant association between rs187084 and SLE risk in an Asian population (for C vs. T: OR?=?0.81, P?=?0.117; for CC vs. TT: OR?=?0.71, P?=?0.158; for CT vs. TT: OR?=?0.86, P?=?0.085; for CC?+?CT vs. TT: OR?=?0.78, P?=?0.093; for CC vs. CT?+?TT: OR?=?0.81, P?=?0.285). Similar results were found between rs352139 and SLE. No significant association was detected in any genetic model in the Asian population either (for G vs. A: OR?=?1.11, P?=?0.095; for GG vs. AA: OR?=?1.32, P?=?0.238; for GA vs. AA: OR?=?1.17, P?=?0.084; for GG?+?GA vs. AA: OR?=?1.17, P?=?0.073; for GG vs. GA?+?AA: OR?=?1.17, P?=?0.404). We found no association between TLR9 gene rs352140 polymorphism and SLE in the Asian population (for A vs. G: OR?=?1.02, P?=?0.728). In conclusion, there is still not enough evidence to indicate an association between TLR9 gene rs187084, rs352139, and rs352140 polymorphisms and the development of SLE in the Asian population.     

IL-15 Gene Polymorphism in Celiac Disease Patients and Their Siblings

BackgroundCeliac disease (CD) is an immune-mediated enteropathy characterized by lifelong gluten intolerance. Interleukin-15 (IL-15) is a proinflammatory cytokine that is considered a key component in the immune reaction triggered by gluten. Our aim of this study was to evaluate the influence of IL-15 gene polymorphisms on CD development and clinical presentation.MethodsThe study was enrolled-with 90 CD patients (49 female/41 male, median years of age 11), their 38 siblings (20 female/18 male, median years of age 8), and 99 healthy controls (66 female/33 male, median years of age 13). Their demographic findings, symptoms, and signs histopathological grade, Human Leukocyte Antigen (HLA) types were recorded. IL-15 gene polymorphisms rs2857261, rs10519613, and rs1057972 were analyzed through PCR.ResultsThere was a significantly higher frequency of GG genotype in rs2857972 polymorphisms and TT genotype in rs1057972 polymorphisms in celiac families compared to controls [41% vs. 23% (P = .0008), 36% vs. 11% (P = .001), respectively]. Without considering their HLA status, there was not any difference between celiacs and healthy siblings. However, when stratified according to their HLADQ2 status, rs2857972 GG polymorphism was 1.5 times prominent in celiacs than siblings at homozygous state, whereas rs1057972 TT genotype was found to be 2.5 times prominent in celiac siblings at heterozygous state. There was no association between these polymorphisms and clinical presentation.Conclusionrs2857972 GG and rs1057972 TT variants of IL 15 are more prominent in celiac families than controls. However, the impact of IL-15 gene polymorphism on CD development is dependent on HLADQ2 status.     

Association of gene expression involving innate immunity and genetic variation in interleukin 28B with antiviral response

Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphisms (SNPs) of IL28B and host response to peginterferon α (PEG-IFNα) and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in IL28B genotypes and elucidate its relation to response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFNα-2b/RBV and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and USP18), and IL28 (IFNλ). Both IL28B SNPs were 100% identical; 54 patients possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral sensors and modulators in IL28B minor patients were significantly up-regulated compared with that in IL28B major patients (≈ 3.3-fold, P < 0.001). However, expression of IPS-1 was significantly lower in IL28B minor patients (1.2-fold, P = 0.028). Expressions of viral sensors and modulators were significantly higher in nonvirological responders (NVR) than that in others despite stratification by IL28B genotype (≈ 2.6-fold, P < 0.001). Multivariate and ROC analyses indicated that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were independent factors for NVR. IPS-1 down-regulation in IL28B minor patients was confirmed by western blotting, and the extent of IPS-1 protein cleavage was associated with the variable treatment response. CONCLUSION: Gene expression involving innate immunity is strongly associated with IL28B genotype and response to PEG-IFNα/RBV. Both IL28B minor allele and higher RIG-I and ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR.