IL-23R基因多态性与炎症性肠病的相关性

目的:研究我国炎症性肠病患者IL-23R基因单核苷酸多态性特征,探讨其与炎症性肠病(IBD)的相关性.方法:采用PCR扩增和测序的方法对198例IBD患者和100名健康体检者(对照组)IL-23R基因3个非同义单核苷酸多态性(rs11209026,p.Arg381Gln;rs41313262,p.Val362Ile;rs11465797,p.Thr175Asn)进行分析,分别计算其等位基因的表现频率,并结合临床资料评估其多态性与IBD的相关性.结果:(1)IBD中克罗恩病(CD)患者IL-23RArg-381Gln等位基因A的表现频率为2.70%,低于对照组(6.00%),但无统计学差异,溃疡性结肠炎(UC)患者的表现频率为5.65%,与对照组无统计学差异;(2)IBD中CD患者IL-23RVal-362Ile等位基因A的表现频率为2.70%,UC组为2.42%,对照组为2.00%,3组间无明显统计学差异;(3)IBD及对照组中均无Thr175Asn等位基因A表现,相应位点均表现为C.结论:我国IL-23R单核苷酸多态性与IBD无明显相关性,遗传异质性可能决定了IBD的易感性.     

IL-17基因多态性与中国汉族人群炎症性肠病的关系

目的:研究IL-17A和IL-17F的5个多态性位点与中国汉族人炎症性肠病之间的关系.方法:采用病例-对照研究方法,收集确诊的溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)患者共350例(UC270例;CD80例),健康对照组268例,收集外周血标本2mL,提取DNA,运用LDR(ligasedetection reaction allelic)技术进行多态性检测.采用SPSS17.0软件进行数据分析.结果:CD患者中IL-17F(rs763780,7488T/C)突变等位基因C的频率明显高于对照组(13.8%vs8.4%,P=0.044,OR=1.74,95%CI1.01-2.99).在亚型分析中,rs763780基因多态性与CD病变范围有关,突变等位基因C在CD回结肠型患者中的频率明显高于对照组(P=0.02).IL-17A(rs2275913,G-197A)与UC患者疾病的严重程度有弱相关性,含有突变基因A的患者倾向于临床轻型.IL-17F(rs763780,7488T/C)多态性与U C患者发病年龄之间有弱相关性,T/C基因型患者趋向于年轻型(P=0.046).结论:IL-17F rs763780基因多态性与CD易感性之间有弱相关性,在亚组分析中发现rs763780与CD的病变范围和UC的发病年龄有关.IL-17A rs2275913基因多态性与UC疾病严重程度呈负相关.     

Association between inflammatory gene polymorphisms and coronary artery disease in an Indian population

Background Inflammation is one of the major components of atherosclerosis which is the underlying disorder that leads to various diseases including coronary artery disease (CAD). Genes that are involved in the inflammatory processes are therefore good candidates for the risk of CAD. Variations in the genes involved in various molecular pathways of inflammation have been implicated to exaggerated atherosclerosis and the risk of cardiovascular diseases. In this study, we performed a genetic association study on the single nucleotide polymorphisms (SNPs) present in the genes CD14 (−159 C/T), TNFα (−308 G/A), IL-1α (−889 C/T), IL-6 (−174 G/C), PSMA6 (−8 C/G), and PDE4D (SNP83 T/C, respectively) in order to discern their possible role in the susceptibility to CAD in a North Indian population. Methods Angiographically proven CAD patients (n = 210) and age, sex and ethnically matched normal healthy controls (n = 232) were recruited for this case-control study. Genotypes were determined by PCR–RFLP method. Chi-square and logistic regression analyses were performed to compare the genotype and allele frequencies between the patient and the control groups. Results None of the SNPs showed significant association with CAD in the study population before and after adjustment for the confounding risk factors like age, sex, hypertension, smoking habit, and diabetes. Conclusion This study was unable to demonstrate any association between the six gene variants tested and CAD in the North Indian population.     

Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population

BACKGROUND AND AIMS: The genetic contribution to inflammatory bowel disease (IBD) is under investigation. Recent evidence indicates a significant linkage between a locus on chromosome 19p13 and IBD. We investigated the association between an intercellular adhesion molecule 1 gene (ICAM-1) polymorphism located on chromosome 19p13 and IBD in a Japanese population. METHODS: We compared 207 Japanese patients who had IBD (79 with Crohn's disease (CD); 128 with ulcerative colitis (UC)) with 103 unrelated Japanese controls. We determined R241G and K469E polymorphisms of the ICAM-1 gene using polymerase chain reaction (PCR) techniques. RESULTS: Both frequency and carriage rate of the K469 allele were significantly higher in IBD patients than in controls (allelic frequency, p(c)=0.0026; carriage rate, p(c)=0.0034; odds ratio 2.59; 95% confidence interval 1.42-4.68). Furthermore, the frequency of the K469 allele was significantly increased in both CD and UC. Subgroup analysis demonstrated that both K469 allelic frequency and K469 carriage rate were significantly higher in patients with the small bowel and colon type of CD and entire colitis compared with healthy controls. CONCLUSIONS: We identified an overall association between IBD and ICAM-1 K469 in a Japanese population. Further studies of this chromosome region are required to elucidate the gene responsible for IBD.     

Association of MYO9B gene polymorphisms with inflammatory bowel disease in Chinese Han population

AIM: To explore the association of MYO9B gene polymorphisms with clinical phenotypes and intestinal permeability of individuals with inflammatory bowel disease (IBD) in China.METHODS: A total of 442 IBD patients and 402 healthy volunteers were genotyped for two single nucleotides (rs962917 and rs1545620) using the ligase detection reaction and polymerase chain reaction. Allelic and genotype frequency analyses were performed for the two groups. Intestinal permeability was evaluated using lactulose (L) and mannitol (M) excretion. The association of MYO9B gene polymorphisms with intestinal permeability between the normal and high intestinal permeability groups was analyzed.RESULTS: Overall, there was no significant difference in the genotypic and allelic frequencies of MYO9B between IBD patients and controls. Although no association was found with ulcerative colitis in the comparison between the subgroups, the frequencies of rs962917 and rs1545620 were different in the Crohn’s disease (CD) subgroup with ileocolitis (CC vs CT and TT, P = 0.014; and AA vs AC and CC, P = 0.022, respectively). rs1545620 variants appear to be the genetic susceptibility factor for perianal disease in CD patients (AA vs AC CC, P = 0.029). In addition, the L/M ratio was significantly higher in IBD patients than in controls (0.065 ± 0.013 vs 0.020 ± 0.002, P = 0.02), but no association was found between the MYO9B gene and the L/M ratio in IBD patients.CONCLUSION: MYO9B gene polymorphisms may influence the sub-phenotypic expression of CD in China. No association between these MYO9B polymorphisms and intestinal permeability in IBD patients was found.     

Association of IL-13 gene polymorphisms with airway hyperresponsiveness in a Japanese adult asthmatic population

BackgroundA single nucleotide polymorphism (SNP; rs20541) in the IL-13 gene has been recognized as a risk factor for asthma. This SNP causes Arg to Gln (Q) substitution at position 110 in the mature IL-13 protein. We have recently showed that FEV1 in asthmatics with the Q110 variant of IL-13 declined faster, and progressive airway remodeling was observed in these subjects (Wynn, 2003 [1]). However, the effects of the IL-13 variant on airway hyperresponsiveness (AHR) remain to be elucidated.We analyzed the relationship between SNP rs20541 in IL-13 and AHR in asthmatics.MethodsWe recruited 182 asthmatics who visited the asthma outpatient clinic at Iwate Medical University Hospital from 2006 to 2011. Subjects were genotyped for rs20541. Asthma severity, atopic status, age of asthma onset, serum IgE concentration, AHR, and pulmonary function were studied in these subjects. AHR was measured using the continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan).ResultsGenotyping of rs20541 revealed 26 A/A, 77 A/G, and 79 G/G patient genotypes. The D min (U) of the 3 genotypes was 1.17±0.300 in A/A, 1.99±0.35 in A/G, and 2.85±0.39 in G/G. The D min in the 3 genotypes was significantly different.Spirometric data revealed that % FEV₁ and % FEF₇₅ were significantly different among the 3 groups of IL-13 genotypes, whereas no significant differences were observed in therapeutic steps, atopic status, house dust mite sensitization, or serum IgE concentration.ConclusionThe SNP rs20541 in IL-13 was associated with AHR in Japanese adult asthmatics.     

Cytokine gene polymorphisms in inflammatory bowel disease.

BACKGROUND: Concordance rates in siblings and twins provide strong evidence that genetic susceptibility is important in the pathogenesis of inflammatory bowel disease. The number and identity of susceptibility genes is largely uncertain. Cytokine genes are attractive candidate loci. AIMS: To study allelic frequencies of polymorphisms of the interleukin-1 receptor antagonist (IL-1RA) gene and the tumour necrosis factor alpha gene in patients with inflammatory bowel disease. SUBJECTS: One hundred and twenty nine North European caucasoid patients with ulcerative colitis, 120 patients with Crohn's disease, and 89 healthy controls. METHODS: Genotyping was performed by polymerase chain reaction. A variable number of tandem repeats (VNTR) in the IL-1RA gene and a single base pair polymorphism in the TNF alpha gene promoter region (TNF-308) were analysed. RESULTS: No significant differences in IL-1RA VNTR allelic frequencies were noted between Crohn's disease (allele 1: 72.6%, allele 2: 24.7%, allele 3: 2.6%), ulcerative colitis (72.6%, 24.3%, 3.1%, respectively), and controls (76.9%, 20.8% and 2.3%). Some 42.4% of patients with ulcerative colitis and 43.4% patients with Crohn's disease were carriers of allele 2, compared with 34.8% healthy subjects. The TNF2 allele was modestly reduced in Crohn's disease (13.2%), compared with healthy subjects (21.3%; p = 0.04), and ulcerative colitis (21.6%). CONCLUSIONS: The associations demonstrated are modest: these polymorphisms are unlikely to be important determinants of overall disease susceptibility.     

Association of IL-6 gene polymorphisms and COPD in a Spanish population

Interleukin-6 (IL-6) is a potential mediator of systemic effects of Chronic Obstructive Pulmonary Disease (COPD). In the present case-control study we investigated the association of promoter polymorphisms of this gene and COPD in a cohort of 191 patients, smokers without COPD (n=75) and a healthy control population (n=296). Besides spirometry, exercise capacity (6MWD, 6 min walking distance) and body mass index (BMI) were measured in COPD patients. Genotyping of the IL-6 polymorphisms at positions -174, -572 and -597 was performed. The -597G/A and -174G/C polymorphisms were not associated with the disease. However, the -572G/C polymorphism was significantly associated with COPD susceptibility under a dominant model of inheritance. The frequency of the genotypes containing the C allele was significantly lower in the COPD cases (9.9%) compared with the healthy control group (16.9%) and smokers (23.1%), (OR=0.46, p=0.032 and OR=0.28, p=0.012, respectively). The GCG (-597/-572/-174) haplotype was significantly associated with the disease (OR=0.37, p=0.022, COPD cases vs. healthy subjects and OR=0.17, p=0.011, COPD cases vs. smokers). Moreover, a borderline association was also found for the -572G allele and hypoxemia (PaO(2)<60 mmHg) (p=0.05). Our data suggest that the IL-6 -572C allele may confer a diminished risk of developing COPD.     

白介素-18基因-607C/A多态性与子宫内膜异位症的关系

目的探讨白介素-18(IL-18)基因-607C/A多态性与子宫内膜异位症(EDM)的关系。方法选择EDM患者234例(EDM组)、健康妇女215例(对照组),采用聚合酶链反应—焦磷酸测序法检测其子宫内膜中的IL-18基因-607C/A多态性分布情况。结果 EDM组IL-18基因-607C/A多态位点的CC、CA和AA基因型频率分别为34.2%、43.6%、22.2%,等位基因C、A的频率分别为56.0%、44.0%;对照组IL-18基因-607C/A多态位点的CC、CA和AA基因型频率分别为20.5%、48.7%、30.8%,等位基因C、A的频率分别为44.9%、55.1%。IL-18基因-607C/A多态性是EDM发病的独立危险因素(P<0.01);C等位基因携带者患EDM的发病风险增高(P<0.01)。结论 IL-18基因-607C/A多态性与EDM的发病存在相关性,C等位基因是EDM发病的重要遗传学危险因素。     

中国北方汉族人群IL-18基因-607C/A和-137G/C多态与心肌梗死的关联性

目的:近年研究发现白细胞介素-18（Interleukin18,IL-18)在冠心病(CAD)的发生、发展及粥样斑块破裂的过程中起重要作用。本研究探讨IL-18基因-607C/A和-137G/C单核苷酸多态与中国北方汉族人群心肌梗死(MI)的关系。方法: 采用序列特异性引物聚合酶链反应对432例对照组和468例MI患者进行检测,分析IL-18基因-607C/A和-137G/C单核苷酸多态的基因型和等位基因分布情况。结果: IL-18基因-607C/A单核苷酸多态3种基因型（CC型,CA型和AA型）在对照组分布频率分别为20.8 %,50.9 %和28.2 %,在MI组分别为36.3 %,44.9%和18.8%,IL-18基因-607C/A多态和中国北方汉族人群MI的发生显著相关(P<0.05)。IL-18基因-137G/C单核苷酸多态三种基因型（GG型,GC型和CC型）在对照组分布频率分别为71.3 %,26.8 %和1.9 %,在MI组分别为75.2 %,23.9 % 和0.9%,IL-18基因-137G/C单核苷酸多态与中国北方汉族人群MI无相关性(P=0.133)。两组间的基因型分布皆符合Hardy－Weinberg平衡定律。Logistic回归校正性别、年龄、体质量指数、吸烟、高血压病、高脂血症、糖尿病等CAD易患因素后,IL-18基因-607C/A多态仍是MI发病的独立的危险因素(P<0.05)。IL-18基因-607C/A和-137G/C单核苷酸多态组成的CG单体型与和MI的危险性呈正相关,而AC单体型与MI的危险性呈负相关。结论: IL-18基因-607C/A多态与中国北方汉族人群中与MI的发生独立相关。     

Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease

Background and Aims: The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. Methods: In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two‐year period (2004–2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction—restriction fragment length polymorphism (PCR‐RFLP) method. The genotype–phenotype association for these polymorphisms was analyzed. Results: Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype–phenotype association was observed with any mutations. Conclusions: This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.     

TNFalpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency

OBJECTIVES: An altered production of cytokines underlies inflammatory bowel disease (IBD) susceptibility. Various polymorphisms at the IL-10 and TNFalpha gene promoters control cytokine production levels. The influence of these polymorphisms on susceptibility to ulcerative colitis (UC) and Crohn's disease (CD) and their association with clinical features were analyzed. SUBJECTS AND METHODS: Genetic polymorphisms of TNFalpha (-308 G/A) and IL-10 (-1082 G/A, -812 C/T, and -592 C/A) were determined using the LightCycler system with hybridization probes matched with one sequence variant. The study population included 99 UC patients, 146 CD patients, and 343 matched controls. RESULTS: We did not find association between TNFalpha or IL-10 gene polymorphisms and UC or CD susceptibility, though a slight influence of -1082*G allele in UC appearance was observed. In a stratified analysis, a highly significant association between the -1082 AA IL-10 genotype and the steroid dependency was observed in IBD (p < 0.0001), contributing both UC (p = 0.004) and CD (p = 0.003) to this association. In contrast, TNFalpha genotypes did not influence steroid dependency in IBD. Further, the contribution of cytokine genotypes and of clinical features to the appearance of steroid-dependent status (dependent variable) was studied by multivariate analysis. The steroid-dependent phenotype correlated in UC with extensive disease (p = 0.010) and with the low producer -1082 AA IL-10 genotype (p = 0.002) and in CD with penetrating disease (p = 0.010), arthritis (p = 0.011), and the -1082 AA IL-10 genotype (p = 0.006). CONCLUSIONS: The main conclusion is that carriage of the -1082 AA IL-10 genotype (low producer) is a relevant risk factor for developing steroid-dependent IBD.     

Risk factors and gene polymorphisms of inflammatory bowel disease in population of Zhejiang, China

AIM:To identify the risk factors and three single nucleotide polymorphisms(SNPs) of NOD2/CARD15 gene in inflammatory bowel disease(IBD) of the population in Zhejiang,China.METHODS:A case-control study was conducted using recall questionnaire to collect data on demographic,socioeconomic,lifestyle characteristics and dietary behaviors from 136 determined IBD patients and 136 paired healthy controls.COX regression method was used to screen the statistically significant risk factors for IBD.The polymorphisms of...     

Associations between CD24 gene polymorphisms and inflammatory bowel disease:A meta-analysis

AIM: To evaluate the relationships between CD24 gene polymorphisms and the risk of inflammatory bowel disease(IBD), including ulcerative colitis(UC)and Crohn's disease(CD).METHODS: The PubMed, Web of Science and Cochrane Library databases were searched(up to May30, 2014). The search terms "CD24", "inflammatory bowel disease", "Crohn's disease", "Ulcerative colitis","IBD", "CD" or "UC"; and "polymorphism", "mutation"or "variant" were used. Association studies were limited to the English language, but no limitations in terms of race, ethnicity or geographic area were employed.Stata SE12 software was used to calculate the pooled odds ratios(ORs) with 95% confidence intervals(CIs).P 0.05 was considered statistically significant. The information was independently extracted from each eligible study by two investigators. Two common polymorphisms, C170T(rs8734) and TG1527del(rs3838646), in the CD24 gene were assessed.RESULTS: A total of three case-control studies including 2342 IBD patients and 1965 healthy controls were involved in this meta-analysis. The patients and controls were from Caucasian cohorts. The three articles included in this meta-analysis all conformed to Hardy-Weinberg equilibrium. This meta-analysis revealed that there were no significant associations between the two CD24 polymorphisms and the risk for IBD(all P 0.05). However, in a disease subgroup analysis, we found that the CD24 C170 T polymorphism was associated with an increased risk of UC in a dominant model(OR = 1.79, 95%CI: 1.15-2.77, P =0.009) and an additive model(OR = 1.87, 95%CI:1.19-2.93, P = 0.007), but this relationship was not present for CD. The CD24 TG1570 del polymorphism was significantly associated with CD in the additive model(OR = 1.24, 95%CI: 1.01-1.52, P = 0.037).CONCLUSION: Our findings provide evidence that the CD24 C170 T polymorphism might contribute to the susceptibility to UC, and the CD24 TG1527 del polymorphism might be associated with the risk of CD.     

NAT2基因多态性与温州汉族人群炎症性肠病遗传易感性的相关性

目的:探讨温州汉族人群中炎症性肠病(IBD)遗传易感性与N-乙酰基转移酶2(NAT2)基因型多态性的相关性.方法:采用聚合酶链反应-限制性片断长度多态性方法,在119例IBD患者及120例健康对照者中,检测NAT2野生型等位基因(NAT2 4)和3种突变型等位基因(NAT2 5B,6A和7B)的频率.结果:在IBD组中,NAT2 4,NAT2 5B,NAT26A和NAT2 7B等位基因频率分别是55.9%,6.7%,23.5%和13.9%,与正常对照组比较无显著差异.CD组和UC组中各等位基因频率与正常对照组比较无显著差异;将NAT2基因型分为快型、中间型和慢型,分别为35.3%,41.2%和23.5%,与正常对照组比较亦无显著差异;对IBD各组进一步分层,也无显著性差异.结论:NAT2基因型多态性和炎症性肠病遗传易感性无显著性相关.