Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn’s disease

AIM:To investigate the correlation between rs1568885,rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn’s disease(CD).METHODS:One hundred and twenty-six patients diagnosed with CD based on standard clinical,endoscopic,radiological,and pathological criteria were enrolled in this study at the Gastroenterology Unit of the 2nd Department of Surgery and at the Colorectal Unit of the1st Department of Propaedeutic Surgery.Infliximab at a dose of 5 mg/kg was administered intravenously at weeks 0,2,6 and then every 8 wk.Clinical and serological responses were assessed using the HarveyBradshaw Index and serum C-reactive protein(CRP)levels,respectively,and the endoscopic response was evaluated by ileocolonoscopy performed at baseline and after 12-20 wk of therapy.The changes in endoscopic appearance compared to baseline were classified into four categories,and patients were classified as responders and non-responders.Genomic DNA from whole peripheral blood was extracted and genotyping was performed by allele-specific polymerase chain reactions.χ2test with Yate’s correction based on the S-Plus was used to compare the genotype frequencies.RESULTS:Eighty patients(63.49%)were classified as complete and 32(25.39%)as partial responders to infliximab,while 14(11.11%)were primary non-responders.No correlation was found between response to infliximab and patients’characteristics such as age,gender and disease duration.There was consistency between Harvey-Bradshaw index scores and serum CRP levels.The TT genotype of the rs1568885 polymorphism was significantly related to partial response(P=0.024)and resistance to infliximab(P=0.007)while the AT genotype was more frequent in partial responders(P=0.035)and in primary non-responders(P=0.032).Regarding rs1813443,the CC genotype was found to be associated with partial response(P=0.005)and primary resistance(P=0.002)to infliximab while no association was found between the rs4411591 polymorphism and the clinical response to infliximab.CONCLUSION:Based on our results,the rs1568885and rs1813443 polymorphisms are associated with clinical and biochemical response to infliximab in Greek patients with Crohn’s disease.     

MicroRNA gene polymorphisms in pancreatic cancer

MicroRNAs (miRNAs) act as regulators of gene expression via translational repression. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to affect the regulatory capacity of miRNAs by influencing miRNA processing and/or miRNA-mRNA interactions. The purpose of this study was to investigate the association between 2 SNPs commonly found in precursor miRNA and the susceptibility and clinicopathological characteristics of pancreatic cancer. The rs11614913/miR-196a2, rs2910164/miR-146a SNPs were genotyped in 93 patients with pancreatic cancer and in 122 healthy controls. No significant differences in genotype distributions between controls and PC patients were observed. However, rs2910164 GG and rs11614913 CC genotypes and the rs2910164C/rs11614913C and rs2910164G/rs11614913C haplotypes were significantly overrepresented in PC patients with T1 and T2 tumor status than in those with T3 and T4. Our findings suggested that the rs2910164 and rs11614913 SNPs might play a role in pancreatic tumorigenesis, but the molecular mechanism underlying the particular sequence variations in miRNA that can cause aberrant expression remains to be determined.     

Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer

AIM: To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-196a2, miR-27a and miR-146a genes are associated with sporadic colorectal cancer (CRC).METHODS: In order to investigate the effect of these SNPs in CRC, we performed a case-control study of 197 cases of sporadic CRC and 212 cancer-free controls originating from the Central-European Caucasian population using TaqMan Real-Time polymerase chain reaction and allelic discrimination analysis.RESULTS: The genotype and allele frequencies of SNPs were compared between the cases and the controls. None of the performed analysis showed any statistically significant results.CONCLUSION: Our data suggest a lack of association between rs11614913, rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population, a population with an extremely high incidence of sporadic colorectal cancer.     

Meta-analysis of association of microRNAs genetic variants with susceptibility to rheumatoid arthritis and systemic lupus erythematosus

Background:An increasing body of studies has investigated that genetic polymorphisms in microRNA (miRNA) may be related to susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, some results remain controversial. Thus, a meta-analysis was embarked on assessing whether some miRNA polymorphisms are associated with the risk of RA and SLE.Methods:Relevant studies were acquired on PubMed, Web of Science, Cochrane Library, CNKI, and Embase electronic databases from inception to December 2019. The strength of the association of miRNA polymorphisms with the risk of RA and SLE was assessed by odds ratios (ORs) and 95% confidence intervals (CIs).Results:Eligible 20 articles (36 studies) involving 5 miRNAs were enrolled in the meta-analysis. For RA, the polled result showed that there was no significant relationship between miR-146a rs2910164 and RA, but subgroup analysis based on ethnicity demonstrated that CC genotype may be a genetic protect factor for RA in Caucasians (CC vs CG+GG, OR = 0.825, 95% CI: 0.684–0.996, Pz = .045, Ph = .166). Besides, statistical significance of miR-499 rs3746444 (T/C) with susceptibility to RA was observed as well in the overall population, and the association was only significant in Caucasians but not Asians. For SLE, the associations of miR-146a rs2431697 T allele/T-carrier with increased risk of SLE were observed.Conclusions:Our results highlight that miR-499 rs3746444 may contribute to RA susceptibility, particularly in Caucasians. In addition, CC genotype in miR-146a rs2910164 may act as a protector of RA in Caucasians. For SLE, miR-146a rs2431697 (C/T) is most likely to the increased the risk of SLE. These findings do not support the genetic association between miR-196a² rs11614913 and RA/SLE susceptibility, as well as the association of miR-146a rs2910164, miR-146a rs57095329, miR-499 rs3746444 with SLE.     

The Association of Common Functional Polymorphisms in Mir-146a and Mir-196a2 and Hepatocellular Carcinoma Risk: Evidence from a Meta-Analysis

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) located in the miRNAs influence the function of mature miRNAs and may contribute to cancer development. Studies investigating the association between miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. We performed a meta-analysis of all available studies to summarize this situation.Eligible studies were identified by search of electronic databases including PubMed, Embase, and Cochrane library for the period up to August 2014. The association of miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).Finally, a total of 12 studies with 4171 cases and 4901 controls were included for miR-146a rs2910164 polymorphism and 10 studies with 4687 cases and 4990 controls were available for miR-196a2 rs11614913 polymorphism. With respect to miR-146a rs2910164 polymorphism, statistical significant increased HCC risk was found when all studies were pooled into the meta-analysis (GG+CG vs CC: OR = 1.097, 95% CI 1.005–1.197, P = 0.037). In subgroup analyses by ethnicity, source of control, and HWE in controls, significant increase of HCC risk was found in Asians, population-based studies, and studies consistent with HWE, but not in Caucasians, hospital-based studies, and studies inconsistent with HWE. With respect to miR-196a2 rs11614913 polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses.The results suggest that the miR-146a rs2910164 polymorphism contributes to increased HCC susceptibility, especially in Asian populations. Further large and well-designed studies are required to validate this association.     

Association between genetic variants in pre-miRNA and colorectal cancer risk in a Chinese population

Introduction

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA expression levels or processing and then contribute to the susceptibility of cancer development. We hypothesized that SNPs in pre-miRNAs may be associated with the risk of colorectal cancer (CRC).

Materials and methods

We genotyped four common polymorphisms (i.e., rs11614913, rs3746444, rs2910164, and rs2292832) in pre-miRNAs of 353 CRC patients and 540 healthy controls to investigate the association between the SNPs and the risk of CRC using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay.

Results

The rs11614913 CT, TT genotypes, and T allele were associated with an increased risk of CRC compared with the CC genotype and C allele (CT vs. CC: OR = 7.34, 95 % CI 3.76–14.34; TT vs. CC: OR = 13.66, 95 % CI 6.76–27.6; T vs. C: OR = 1.99, 95 % CI 1.63–2.42, respectively). Interestingly, using the rs2910164 GG genotype as a reference, the rs2910164 GC genotype was associated with an increased risk of CRC (OR = 1.49, 95 % CI 1.02–2.18), whereas the rs2910164 CC genotype was associated with a decreased risk of CRC (OR = 0.58, 95 % CI 0.37–0.93). When compared with the rs2910164G allele, rs2910164 C allele was associated with a reduced risk of CRC (OR = 0.80, 95 % CI 0.66–0.97, p = 0.02).

Conclusion

These findings suggest that rs11614913 and rs2910164 polymorphisms may be associated with the etiology of CRC.     

MiR-146a rs2910164 polymorphism increases risk of gastric cancer: A meta-analysis

AIM: To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer.METHODS: A comprehensive electronic search was conducted for articles published up until January 27, 2014 in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and Google Scholar. Only case-control studies published in English that evaluated the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer were included. Furthermore, only studies with sufficient data allowing for calculation of odds ratio (OR) and corresponding 95% confidence interval (CI) were included. These values were used in the quantitative synthesis to assess the strength of the association between the miR-146a rs2910164 polymorphism and risk of gastric cancer.RESULTS: The database search identified 1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls) were included for the meta-analysis. The results indicate that miR-146a rs2910164 polymorphism is more likely to be associated with gastric cancer risk. In the overall analysis, a significantly increased cancer risk was found in the heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for pooled OR). In the ethnicity subgroup analysis, a similar result was found among Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the stratified analysis by quality of studies, a significantly increased cancer risk was found in the heterozygote comparison among high quality studies (OR = 1.12, 95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample size, a significantly increased cancer risk was found among small sample size subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01), homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons.CONCLUSION: The miR-146a rs2910164 polymorphism is associated with increased gastric cancer risk, particularly evident in high quality studies with small sample sized Caucasian populations.     

肥胖原发性高血压伴高胰岛素血症患者血管紧张素原基因rs7079变异与福辛普利降压疗效的关系

目的 分析血管紧张素原（AGT）基因rs7079（C／A）与福辛普利在伴高胰岛素血症的肥胖原发性高血压（EH）患者中降压疗效的相关性。方法以福辛普利（10mg,1次／d）治疗70例伴高胰岛素血症的肥胖EH患者,疗程4周。检测AGT基因rs7079（C／A）的基因型,分析其与降压效果及IS相关指标的关系。结果AGT基因rs7079（C／A）位点C、A等位基因频率分别为77．14％、22．86％,其中,CC基因型患者43例,AC＋AA基因型患者27例。与治疗前相比,两组基因型患者治疗4周后SBP、DBP均下降（P〈0．05）,CC基因型患者SBP低于AC＋AA基因型患者[（126．16±1．93）vs（133．00±2．40）mmHg,P〈0．053。未发现AGT基因rs7079（C／A）基因型与IS有相关性。结论肥胖EH伴高胰岛素血症患者AGT基因rs7079（c／A）与福辛普利降压疗效相关,其中,cc基因型患者降SBP效果更好。     

Association Study of Genetic Variants in miRNAs in Patients with Inflammatory Bowel Disease: Preliminary Results

Background

Aberrant expression and structural alteration of miRNAs are considered to participate in inflammation and cancer development. It has been suggested that common single-nucleotide polymorphisms (SNPs) in miRNAs are associated with susceptibility to several human diseases.

Methods

In the present preliminary study we evaluated the associations of two SNPs (rs2910164 and rs11614913 in miR-146a and miR-196a2, respectively) with the risk of inflammatory bowel disease (IBD) in a Greek population.

Results

The rs2910164 and rs11614913 SNPs were genotyped in 242 patients with Crohn’s disease (CD), 210 patients with ulcerative colitis (UC) and 300 healthy individuals. No statistically significant differences were found in the genotype or allele distributions of the rs2910164 SNP among UC and control subjects. However, significant differences were found in the genotype or allele distributions of the rs2910164 polymorphism among CD and control subjects (P < 0.0001 and P < 0.0001, respectively). Concerning the rs11614913, no statistically significant differences were found in the genotype or allele distributions among CD and control patients, whereas TT genotype and T allele seem to have a protective role against UC (P = 0.017 and P = 0.007, respectively). The presence of rs2910164 and rs11614913 SNPs did not influence disease phenotype.

Conclusions

Our results demonstrate that the rs2910164 polymorphism has a major role in genetic susceptibility to CD but not to UC, since the rs11614913 polymorphism had a protective role against UC, at least in the population studied here. Independent studies are needed to validate our findings in larger series and in patients of different ethnic origins.     

Associations between PTPRC rs10919563 A/G and FCGR2A R131H polymorphisms and responsiveness to TNF blockers in rheumatoid arthritis: a meta-analysis

We aimed to investigate whether the PTPRC rs10919563 A/G and Fc gamma receptor 2A (FCGR2A) R131H polymorphisms can predict the response to anti-TNF therapy in rheumatoid arthritis (RA) patients. We conducted a meta-analysis of studies on the association between the PTPRC rs10919563 A/G or the FCGR2A R131H polymorphism and responsiveness to anti-TNF therapy in RA patients. Eighteen studies (twelve on PTPRC and six on FCGR2A) from eight articles involving 3058 patients were considered in this meta-analysis. The meta-analysis showed a significant association between the PTPRC rs10919563 A allele and response to TNF-α blockers in RA. The OR of the PTPRC A allele was significantly lower in responders (OR = 0.584, 95 % CI = 0.409–0.835, P = 0.003). Meta-analysis revealed no association between the FCGR2A HH + HR genotype and responsiveness to TNF blockers in all study subjects (OR = 0.762, 95 % CI = 0.543–1.068, P = 0.115). However, stratification by TNF inhibitor type showed that the FCGR2A HH + HR genotype was associated with responsiveness to adalimumab (OR = 0.591, 95 % CI = 0.369–0.947, P = 0.029), but not infliximab and etanercept (OR = 0.929, 95 % CI = 0.354–2.440, P = 0.881; OR = 0.804, 95 % CI = 0.293–2.207, P = 0.673). The PTPRC rs10919563 A allele shows a poor response to anti-TNF therapy, and the FCGR2A HH + HR genotype shows a poor response to adalimumab for RA. Genotyping for these polymorphisms may be useful for predicting the response to TNF-α blockers with respect to personalized medicine.     

rs12122341多态性与中国汉族人缺血性卒中发病风险无关

目的 探讨rs12122341多态性与中国汉族人群缺血性卒中及其主要亚型的相关性.方法 纳入来自中国汉族人群的缺血性卒中患者和健康对照者,采用改良多重高温连接酶法检测rs12122341基因型.结果 共纳入776例缺血性卒中患者(大动脉粥样硬化性卒中415例,小动脉闭塞性卒中361例)和776例健康对照者.基因分型显示,在所有研究对象中仅检测到rs12122341CC和CG 2种基因型,未检测到GG基因型.病例组等位基因和基因型频率与对照组均无显著性差异.多变量logistic回归分析显示,rs12122341多态性与缺血性卒中[优势比(odds ratio,OR) 1.482,95％可信区间(confidence interval,CI)0.641～3.421;P=0.447]、大动脉粥样硬化性卒中(OR 1.972,95％ CI0.655 ～6.034;P=0.227)和小动脉闭塞性卒中(OR1.632,95％CI0.437 ～6.262;P=1.000)均无显著相关性.结论 在中国汉族人群中,rs12122341多态性与缺血性卒中及其主要亚型均无显著相关性.     

Do SNPs in folate pharmacokinetic pathway alter levels of intracellular methotrexate polyglutamates and affect response? A prospective study in Indian patients

This study investigated the impact of seven polymorphisms in genes of folate transport and (de)glutamation pathway on methotrexate polyglutamate levels and response in patients with rheumatoid arthritis. This prospective study included patients with rheumatoid arthritis. They were treated with methotrexate (up to 25 mg per week) for 24 weeks and categorized by EULAR response criteria into responders (good and moderate) and non-responders. Using real-time Taqman discrimination assay, SNPs were genotyped—rs1045642 (ABCB1 3435C>T), rs1128503 (ABCB1 1236C>T), rs10106 (FPGS 1994A>G), rs1544105 (FPGS G>A), rs11545078 (GGH 452C>T), rs3758149 (GGH -401C>T), and rs1051266 (RFC1 80G>A). RBC methotrexate polyglutamate_1–5(MTX-glu_1–5) levels were determined at 4, 8, 16, and 24 weeks using by reverse phase HPLC using C-18 column followed by post column photo-oxidation. This study included 117 patients with rheumatoid arthritis (M:F?=?14:103). The mean dose of methotrexate at 24 weeks was 22.0?±?4.0 mg, with data on DAS28(3) at 24 weeks available in 96 patients—61 responders and 35 non-responders. Minor allele of GGH 452C>T had an association with non-response (odds ratio 2.9, 95% CI 1.4–5.6) and assuming the dominance of C, the recessive genetic model found GGH 452C>T CC genotype (odds ratio 9.5, 95% CI 1.2 to 76.0) was significantly associated with response. However, there was no difference in MTX-glu_1–5 levels among the various genotypes of this SNP (p?=?0.9). Other SNPs were neither associated with response nor with alteration in methotrexate polyglutamate levels. On logistic regression, GGH 452C>T CC genotype and DAS28(3) at baseline were independent predictors of response. GGH 452C>T CC genotype was associated with response to methotrexate. None of the SNPs affected MTX-glu_1–5levels.     

C反应蛋白单核苷酸多态性与睡眠呼吸暂停综合征患者合并高血压的关系

目的：探讨C反应蛋白（CRP）单核苷酸多态性与阻塞性睡眠呼吸暂停综合征（OSAHS）合并高血压的关系。方法2006年1月至2012年12月间于解放军总医院行多导睡眠检查,结果为重度OSAHS的300例男性患者,其中OSAHS伴高血压者145例,并随机抽取100例健康男性对照,采用基因测序的方法,检测CRP启动区基因rs3091244和rs1205的基因多态性。采用R×C列联表χ2检验统计OSAHS伴高血压组、单纯OSAHS组以及健康对照组之间CRP基因多态性的关系。结果 OSAHS合并高血压组rs3091244的CT型基因比例增高,为17%,而单纯OSAHS组为7%。并且rs3091244的T等位基因频率在OSAHS合并高血压组中也明显增高,为9%,而单纯OSAHS组为3%。rs1205的CC基因型在OSAHS合并高血压组中明显升高,为25%,而单纯OSAHS组为11%。结论 CRP的单核苷酸多态性与OSAHS合并高血压有关,rs3091244的CT型基因和rs1205的CC型基因可能通过增加血清CRP水平,引起体内慢性炎症,从而在高血压的发生中产生作用。     

Functional FCGR3A 158 V/F and IL-6 −174 C/G polymorphisms predict response to biologic therapy in patients with rheumatoid arthritis: a meta-analysis

The aim of this study was to investigate whether the Fc gamma receptor 3A (FCGR3A) 158 V/F and interleukin-6 (IL-6) promoter ?174 G/C polymorphisms can predict the response to biologic-based therapy in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between the FCGR3A V/F polymorphism or the IL-6 ?174 C/G polymorphism and non-responsiveness to biologic therapy in RA patients. A total of 10 studies involving 1,427 patients were considered. These studies consisted of seven studies on the FCGR3A polymorphism and three studies on the IL-6 polymorphism. Meta-analysis showed no association between the FCGR3A VV+VF genotype and non-responders to biologic therapy [odds ratio (OR) 0.881, 95 % confidence interval (CI) 0.505–1.537, p = 0.655]. However, stratification by biologic type indicated an association between the FCGR3A VV+VF genotype and non-responders to rituximab (OR 0.566, 95 % CI 0.373–0.857, p = 0.007), but no association was found in non-responders to tumor necrosis factor (TNF)-blockers (OR 1.337, 95 % CI 0.869–2.056, p = 0.186). Meta-analysis revealed no association between the IL-6 CC+CG genotype and non-responders to the biologics (OR 3.233, 95 % CI 0.766–13.64, p = 0.110). However, an association was found between the IL-6 CC+CG genotype and non-responders to anti-TNF therapy (OR 8.030, 95 % CI 1.807–33.68, p = 0.006). This meta-analysis demonstrates that FCGR3A V allele carriers show a better response to rituximab, and individuals carrying the IL-6 ?174 C allele show a poorer response to anti-TNF therapy for RA. Genotyping for these polymorphisms may be a useful tool for predicting the response to biologics with respect to personalized medicine.     

Genetic polymorphisms predict response to anti-tumor necrosis factor treatment in Crohn's disease

AIM To investigate genetic factors that might help define which Crohn's disease(CD) patients are likely to benefit from anti-tumor necrosis factor(TNF) therapy. METHODS This was a prospective cohort study. Patients wererecruited from a university digestive disease practice database. We included CD patients who received antiTNF therapy,had available medical records(with information on treatment duration and efficacy) and who consented to participation. Patients with allergic reactions were excluded. Patients were grouped as ever-responders or non-responders. Genomic DNA was extracted from peripheral blood,and 7 single nucleotide polymorphisms(SNPs) were assessed. The main outcome measure(following exposure to the drug) was response to therapy. The patient genotypes were assessed as the predictors of outcome. Possible confounders and effect modifiers included age,gender,race,and socioeconomic status disease,as well as disease characteristics(such as Montreal criteria). RESULTS121 patients were included. Twenty-one were nonresponders,and 100 were ever-responders. Fas ligand SNP(rs763110) genotype frequencies,TNF gene-308 SNP(rs1800629) genotype frequencies,and their combination,were significantly different between groups on multivariable analysis controlling for Montreal disease behavior and perianal disease. The odds of a patient with a Fas ligand CC genotype being a non-responder were four-fold higher as compared to a TC or TT genotype(P = 0.009,OR = 4.30,95%CI: 1.45-12.80). The presence of the A(minor) TNF gene-308 allele correlated with three-fold higher odds of being a non-responder(P = 0.049,OR = 2.88,95%CI: 1.01-8.22). Patients with the combination of the Fas ligand CC genotype and the TNF-308 A allele had nearly five-fold higher odds of being a non-responder(P = 0.015,OR = 4.76,95%CI: 1.35-16.77). No difference was seen for the remaining SNPs.CONCLUSION The Fas-ligand SNP and TNF gene-308 SNP are associated with anti-TNF treatment response in CD and may help select patients likely to benefit from therapy.     

PR方案治疗慢性丙型肝炎患者ITPA基因rs1127354位点多态性与利巴韦林相关性溶血关系探讨*

目的 探讨应用标准抗病毒(PR)方案治疗慢性丙型肝炎(CHC)患者三磷酸次黄嘌呤核苷(ITPA)基因多态性对抗病毒疗效及其对利巴韦林(RBV)相关性溶血的影响。方法 2016年3月~2018年3月我院收治的CHC患者235例,给予聚乙二醇化干扰素α-2a联合RBV治疗24～48 w。采用基因测序法检测血ITPA基因rs1127354位点多态性。结果 经检测,发现ITPA基因型rs1127354位点为CC型193例和AA/AC型42例;在完成24周疗程的188例(CC型152例和AA/AC型36例)CHC患者中, AA/AC型患者快速病毒学应答和早期病毒学应答率分别为44.4%和47.2%,与CC型的42.1%和42.7%比,无显著性差异(P>0.05),而持续病毒学应答率为72.2%,显著高于CC型的53.3%(P<0.05);在治疗4周、8周、12周和24周,AA/AC型患者Hb水平分别为(138.2±14.7) g/L、(130.5±12.6) g/L、(123.7±12.5)g/L和(118.0±10.2)g/L,显著高于CC型【分别为(132.3±13.9)g/L、(113.1±10.5)g/L、(108.4±9.4)g/L和(106.7±11.3)g/L,P＜0.05】。结论 在PR方案治疗的慢性丙型肝炎患者,ITPA基因(rs1127354)CC基因型较AA/AC基因型更易发生RBV 相关性溶血,而ITPA基因型与抗病毒效果密切相关,临床应加以重视和预防性处理。     

Association of two polymorphisms of the IL28B gene with viral factors and treatment response in 1,518 patients infected with hepatitis C virus

Background

Two nucleotide polymorphisms of the interleukin-28B (IL28B) gene, at rs8099917 and rs12979860, influence the response to interferon (IFN)-based therapies in patients infected with hepatitis C virus (HCV) of genotype 1. We aimed to investigate whether these polymorphisms showed complete linkage in Japanese patients.

Methods

A total of 1,518 Japanese patients infected with HCV were genotyped for the two IL28B loci, and the two sets of genotypes were compared.

Results

TT at rs8099917 and CC at rs12979860 were detected in 77.7 and 76.8%, respectively, of the 1,518 patients and TG/GG and CT/TT were detected in 22.3 and 23.2%. These two sets of IL28B genotype stood in strong linkage disequilibrium (r ²?=?0.98). Discordance between the two IL28B polymorphisms occurred in 16 (1.1%) patients, and 13 (0.9%) of them possessed IFN-sensitive TT at rs8099917 and IFN-resistant CT at rs12979860. Three of these 13 patients had HCV of genotype 1b and had received pegylated-interferon and ribavirin, and none of them gained a sustained virological response. At rs8099917, IFN-resistant TG/GG were more frequent in patients infected with HCV of genotype 1 than in those infected with HCV of genotype 2 [258/1,046 (24.7%) vs. 75/441 (17.0%), p?=?0.001]. The response to pegylated-interferon/ribavirin in 279 patients who were infected with HCV-1 and the response to IFN monotherapy in 361 patients who were infected with HCV-1 , was higher in those with TT than in those with TG/GG at rs8099917, as well as being higher in those with CC than in those with CT/TT at rs12979860 (p?Conclusions Linkage disequilibrium between two IL28B polymorphisms at rs8099917 and rs12979860 is strong in Japanese HCV patients, but there are some discrepancies between the two sets of genotypes.     

Association of XPG rs2094258 polymorphism with gastric cancer prognosis

BACKGROUND The xeroderma pigmentosum group G(XPG)gene at chromosome 13q33 consists of 15 exons,which may be related to the occurrence and development of gastric cancer(GC).AIM To examine the association of several common single nucleotide polymorphisms(SNPs)of the XPG gene with GC risk and survival.METHODS Five SNPs of XPG(rs2094258,rs751402,rs873601,rs2296147,and rs1047768)were genotyped by PCR restriction fragment length polymorphism in 956 histologically confirmed GC cases and 1012 controls in North China.GC patients were followed for survival status and,if deceased,cause of death.Logistic regression and Cox regression were used for analysing associations of XPG SNPs with risk of GC and prognosis,respectively.For rs2094258,heterozygous model(CT vs CC),homozygous model(TT vs CC),recessive model(TT vs CT+CC),and dominant model(TT+CT vs CC)were analyzed.RESULTS None of the examined loci were statistically associated with GC risk,although rs2296147 was marginally associated with GC risk(P=0.050).GC patients with the rs2094258 CT+CC genotype showed worse survival than those with the TT genotype(log-rank test,P=0.028),and patients with the CC genotype had a tendency of unfavourable prognosis compared with those with the TT+CT genotype(log-rank test,P=0.039).The increase in C alleles of rs2094258[hazard ratio(HR)=1.19,95%confidence interval(CI):1.02-1.45,P=0.037]were associated with the long-term survival of GC cases.Other risk factors for survival included tumor differentiation(HR=4.51,95%CI:1.99-8.23,P<0.001),lymphovascular invasion(HR=1.97,95%CI:1.44-3.01,P<0.001),and use of chemotherapy(HR=0.81,95%CI:0.63-0.98,P=0.041).CONCLUSION The XPG rs2094258 polymorphism may be associated with overall survival in GC patients.     

The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility

Purpose: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. Methods: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. Results: The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1–2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4–6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC–GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4–8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 – 2], P = 0.01). Conclusions: The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC–GG combined genotype and C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.     

IRAK1 rs3027898 C/A polymorphism is associated with risk of rheumatoid arthritis

IRAK1 and miR-499 play an important role in the etiology of rheumatoid arthritis. Few studies to date have focused on the influence of the IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C polymorphisms in the susceptibility of the Chinese population to rheumatoid arthritis. We hypothesized that these polymorphisms may contribute to rheumatoid arthritis susceptibility. We studied IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C gene polymorphisms in 214 rheumatoid arthritis cases and 478 controls in a Chinese population. Genotyping was performed by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the IRAK1 rs3027898 CC homozygote genotype was used as the reference group, the AA genotype was associated with significantly increased risk of rheumatoid arthritis (odds ratio (OR) = 1.91, 95 % confidence interval (CI) = 1.12–3.26, p = 0.017). A significantly increased risk of RA associated with the IRAK1 rs3027898 AA genotype was more evident among females, younger patients, CRP negative patients and both anti-CCP positive and negative patients compared with the IRAK1 rs3027898 CC/CA genotypes. The hsa-mir-499 rs3746444 T/C single nucleotide polymorphism (SNP) was not significantly associated with the risk for rheumatoid arthritis. Our findings suggest that the functional SNP IRAK1 rs3027898 C/A variant allele is associated with the development of rheumatoid arthritis. However, the hsa-mir-499 rs3746444 T/C polymorphism may not be associated with susceptibility to rheumatoid arthritis.