T300A polymorphism of ATG16L1 and susceptibility to inflammatory bowel diseases:A meta-analysis

AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications addressing the relationship between rs2241880/T300A polymorphism of ATG16L1 and Crohn‘s disease (CD) and ulcerative colitis (UC) were selected from the MEDLINE and EMBASE data-bases. To make direct comparisons between the data collected in these studies, the individual authors were contacted when...     

ATG16L1基因启动子单核苷酸多态性可增加急性心肌梗死的易感性

目的 探讨ATG16L1基因启动子序列单核苷酸多态性(SNP)与急性心肌梗死(AMI)的相关性。方法采用病例-对照研究方法,对285例AMI患者和296例对照人群的ATG16L1基因启动子采用聚合酶链反应扩增片段并测序,结合DNA测序后的序列及比对SNP数据库后进行数据统计和分析。运用Hardy-Weinberg平衡检验后,应用χ²检验和t检验进行相关分析。采用Logistic回归对多种危险因素以及3个SNP位点与AMI易感性进行关联性分析。用Haploview 4.2软件和SHEsis在线软件进行连锁不平衡及单倍型分析。TRANSFAC数据库用于预测可能受SNP影响的转录因子的结合位点。结果 多因素Logistic回归分析结果显示男性、吸烟史、高血压是AMI的独立危险因素(P＜0.05),而高密度脂蛋白胆固醇是AMI的保护因素(P＜0.05)。在ATG16L1基因启动子序列中的3个SNP(rs1816753、rs12476635、rs2289477)中,rs1816753的TC基因型与AMI间存在关联,可明显增加AMI的患病风险(OR=2.519,95%CI:1.130～5.615,P＝0.024)。通过Haploview 4.2软件分析显示3个SNP之间呈强连锁。结论 ATG16L1基因启动子SNP可能与AMI易感性相关,rs1816753的TC基因型可能是AMI的遗传危险因素。     

NOD2,IL23R and ATG16L1 polymorphisms in Lithuanian patients with inflammatory bowel disease

AIM:To investigate the frequency of NOD2, IL23R and ATG16L1 genetic variants in a case-control panel for inflammatory bowel disease (IBD) from Lithuania.METHODS: One hundred and eighty unrelated IBD pa- tients [57 Crohn‘s disease (CD) and 123 ulcerative colitis (UC)] and 186 healthy controls were genotyped for the following known genetic susceptibility variants:NOD2-Arg702Trp (rs2066844), Gly908Arg (rs2066845) and Leu1007insC (rs2066847), as well as IL23R-Arg381Gln (rs11209026) and ATG16L1-Thr300Ala (rs2241...     

Three novel ATG16L1 mutations in a patient with acute myocardial infarction and coronary artery ectasia: A case report

Introduction:Acute myocardial infarction (AMI) is a specific type of coronary artery disease (CAD) caused by the rupture of coronary atherosclerotic plaques. Coronary artery ectasia (CAE) is a rare phenotype of cardiovascular disease that may promote thrombosis and inflammatory responses leading to myocardial infarction due to abnormal dilatation of blood vessels and coronary blood flow disorders. It is a complicated disease and shows interaction between genetic and environmental factors.Patient concerns:A 34-year-old male patient was admitted to our hospital on May 12, 2016, with complaints of chest pain for 1 hour duration.Diagnosis:Coronary angiography through the emergency medical service (EMS) system showed 100% occlusion at the first turning point of the right coronary artery (RCA), along with tumor-like expansion of the proximal segment of the RCA and the end of the left main (LM) artery. The patient was diagnosed with AMI and CAE. Three-point mutations in the ATG16L1 gene were identified by direct sequencing.Interventions:After admission, the patient underwent emergency green channel coronary angiography and percutaneous coronary intervention (PCI) to assess and unblock the stenosis and occlusion of the RCA lumen, but no stenting was performed because the catheter could not pass the second inflection point of the RCA. Aspirin enteric-coated tablets, clopidogrel sulfate tablets, tirofiban hydrochloride, and low molecular weight heparin calcium were given as anticoagulant and antiplatelet therapy. Atorvastatin calcium tablets were used to regulate blood lipid levels. Perindopril and spironolactone were used to inhibit the renin-angiotensin-aldosterone system (RAAS) to reverse myocardial remodeling. Acetylcholinesterase inhibitors (ACEI) and beta blockers were administered to resist ventricular remodeling and improve cardiac function and prognosis after the patient''s blood pressure and heart rhythm were stabilized.Outcomes:After active rescue treatment, the patient recovered and was discharged. A coronary angiogram performed 2 years later showed that the RCA blood flow was restored, and the patient had recovered well.Conclusion:Three-point mutations in the ATG16L1 gene were identified in a patient with AMI and CAE, which extended the mutation spectrum of the ATG16L1 gene. Hence, the etiology of coronary artery aneurysmal dilatation is worthy of further investigation.     

A study in three European IBD cohorts confirms that the ATG16L1 c.898A > G (p.Thr300Ala) variant is a susceptibility factor for Crohn’s disease

Background and aimsA recent study reported that a nonsynonymous SNP rs2241880 (c.898A > G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A > G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands.MethodsIn total, we included 910 European IBD patients and compared the ATG16L1 c.898A > G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n = 310; ulcerative colitis [UC] n = 179), Hungary (CD n = 147; UC n = 117), and the Netherlands (CD n = 157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics.ResultsWe found a highly significant association of c.898A > G to CD. The association was significant (p = 0.0005) for the total CD cohort but also for the individual populations from Germany (p = 0.02) and Netherlands (p = 0.02) whereas in the Hungarian CD patients a clear trend was observed (p = 0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A > G and UC. No statistical interactions were observed between ATG16L1 c.898A > G and CARD15 variants. Furthermore no association to a CD subphenotype was detected.ConclusionsWe confirm that ATG16L1 variant c898A > G confers a risk variant for CD but is not associated with a distinct CD phenotype.     

IRGM和ATG16L1基因多态性与中国汉族人群克罗恩病的相关性

目的分析IRGM和ATG16L1基因多态性与中国汉族人群克罗恩病(crohn’s disease,CD)发病的相关性。方法选取中国汉族CD患者和健康对照者各318例纳入研究,采用聚合酶链式反应和直接测序方法检测其IRGM和ATG16L1基因的基因型,比较两组间基因型和等位基因频率。结果 CD组和正常对照组IRGM基因rs13361189位点、ATG16L1基因rs2241880位点基因型和基因频率分布均符合Hardy-Weinberg遗传平衡定律,两组间2种基因相应的SNP位点的基因型和等位基因频率差异均无统计学意义(P>0.05)。结论虽然IRGM和ATG16L1基因的遗传变异与西方白种人CD的易感性相关,但是IRGM和ATG16L1基因多态性却与中国汉族人CD无明显相关性。     

ATG16L1基因多态性与广西壮族人群炎症性肠病的关系

目的研究ATG16L1基因单核苷酸多态性（SNP）位点rs2241880与中国广西壮族炎症性肠病（IBD）易感性的关系。方法分别收集146例中国广西IBD患者[其中溃疡性结肠炎（UC）86例,克罗恩病（CD）60例]与164例正常对照者的肠黏膜组织,用酚一氯仿法提取DNA,采用聚合酶链反应（PCR）扩增ATG16L1基因,PCR产物片段直接进行DNA测序分析,结果在Genbank基因库上进行序列比较。结果UC、CD患者与正常对照组之间ATG16L1基因SNP位点rs2241880的等位基因多态性无统计学差异（P〉0．05）。结论ATG16L1基因SNP位点rs2241880与广西壮族IBD患者的易感性无关。     

Mannose-binding lectin 2 rs11003123 polymor-phism is associated with the development of hepatocellular carcinoma in patients with hepa-titis B-related cirrhosis in the Chinese population

BACKGROUND: Mannose-binding lectin 2 (MBL2) plays a key role in the host immune response, but whether it is associ-ated with hepatocellular carcinoma (HCC) is not clear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus (HBV)-related cirrhosis in the Chinese population.
METHODS: A single-nucleotide polymorphism of MBL2, rs11003123, was genotyped and analyzed in a case-control study of HBV-related cirrhotic patients with HCC (n=77) and without HCC (n=40).
RESULTS: We found that Child-Pugh proifles, model for end-stage liver disease score, and the incidence of encephalopathy were all higher in the non-HCC group (P<0.05). A signiifcant association between allele mutants and HCC occurrence was demonstrated by allele comparison (A vs G) (OR=0.34; 95%CI: 0.15-0.76;P=0.006). Heterozygous comparison (GA vs GG) revealed that the individuals with GA mutants had a reduced risk of HCC occurrence compared with those with GG wild type (adjusted OR=0.28; 95% CI: 0.10-0.80;P=0.004). In a dominant model (GA+AA vs GG), a decreased risk of HCC occurrence was observed in individuals with variant geno-types (GA and AA) compared with those with the wild type (adjusted OR=0.30; 95% CI: 0.11-0.85;P=0.004). However, no statistically signiifcant associations were observed between rs11003123 and prognosis of patients with HCC after liver transplantation in both recurrence-free survival and overall survival (P=0.449 andP=0.384, respectively).
CONCLUSION: MBL2 rs11003123 polymorphism may be a marker for the risk of HCC occurrence in patients with HBV-related cirrhosis in the Chinese population.     

A 4‐gene expression score associated with high levels of Wilms Tumor‐1 (WT1) expression is an adverse prognostic factor in acute myeloid leukaemia

Wilms Tumor‐1 (WT1) expression level is implicated in the prognosis of acute myeloid leukaemia (AML). We hypothesized that a gene expression profile associated with WT1 expression levels might be a good surrogate marker. We identified high WT1 gene sets by comparing the gene expression profiles in the highest and lowest quartiles of WT1 expression in two large AML studies. Two high WT1 gene sets were found to be highly correlated in terms of the altered genes and expression profiles. We identified a 17‐probe set signature of the high WT1 set as the optimal prognostic predictor in the first AML set, and showed that it was able to predict prognosis in the second AML series after adjustment for European LeukaemiaNet genetic groups. The gene signature also proved to be of prognostic value in a third AML series of 163 samples assessed by RNA sequencing, demonstrating its cross‐platform consistency . This led us to derive a 4‐gene expression score, which faithfully predicted adverse outcome. In conclusion, a short gene signature associated with high WT1 expression levels and the resultant 4‐gene expression score were found to be predictive of adverse prognosis in AML. This study provides new clues to the molecular pathways underlying high WT1 states in leukaemia.     

IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV‐coinfected patients

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV‐coinfected patients. We carried out a cross‐sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate^® assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.