慢性苯中毒发病风险与XRCC1基因多态性关联的病例对照研究

采集病例组慢性苯中毒(CBP)患者102名、对照组204名人员静脉血,应用PCR探针法和引物延伸SNa Pshot法检测XRCC1 rs25487、rs25489、rs1799782 SNP位点基因型,分析基因多态位点和CBP易感性的关联,以比值比(odds ratio,OR)及其95%可信限(95%confidence interval,95%CI)表示关联强度。结果显示,XRCC1rs25487CT基因型(ORadj=5.146,95%CI=2.441~10.852,χ2=21.098,P0.05)或TT基因型(ORadj=13.985,95%CI=6.440~30.371,χ2=56.316,P0.05)、rs1799782 AA基因型(ORadj=2.012,95%CI=0.926~4.372,χ2=5.100,P0.05)可使CBP发生风险增高,未发现XRCC1 rs25489位点与CBP发生的关联。提示XRCC1 rs25487 CT或TT基因型、rs1799782 AA基因型多态可能作为CPB发病危险性增加的生物学标志之一。     

哺乳动物雷帕霉素靶蛋白复合物1调节相关蛋白基因多态性与肝细胞癌遗传易感性的关联研究

目的探讨广西地区人群哺乳动物雷帕霉素靶蛋白复合物1调节相关蛋白基因(Regulatory Associated Protein Of m TOR,complex 1,RPTOR)潜在功能性单核苷酸多态性位点(Single Nucleotide Polymorphism,SNP)与肝细胞癌(Hepatocellular Carcinoma,HCC)遗传易感性的关系。方法采用以医院为基础的病例对照研究方法,以1 048例HCC患者和1 052例年龄、性别匹配的非肿瘤对照为研究对象,对候选的RPTOR基因潜在功能性SNPs(rs3751934CA、rs1062935 TC、rs3751932 TC及rs12602885 GA),应用Taqman-MGB荧光定量PCR方法进行基因分型。结果未发现RPTOR基因单个SNP位点与HCC遗传易感性之间存在显著性统计学关联;进一步按年龄、性别、民族、吸烟史、饮酒史和乙型肝炎病毒感染等因素进行分层分析,结果发现,在乙型肝炎病毒感染者中,RPTOR rs1062935多态性位点与HCC遗传易感性之间存在显著性统计学关联(OR=1.48,95%CI=1.01~2.18),而且该SNP位点与乙型肝炎病毒感染存在交互作用(Pinteraction=0.048)。结论本研究结果提示RPTOR基因rs1062935位点可能与HBV相关HCC的遗传易感性有关。     

广东汉族人群GLUT4基因多态性与冠心病关系

目的探讨中国广东汉族人群葡萄糖转运蛋白-4(GLUT4)基因多态性与冠心病易感性之间的关系。方法采用多重单核苷酸多态性(SNP)分型试剂盒,对筛选的2个tag SNP位点(rs16956647、rs5435)在1 044例冠心病患者和1 349例非冠心病患者为对照进行基因分型;采用遗传分析软件Plink和统计分析软件SPSS 17.0分析SNP位点与冠心病的关联性。结果 SNP rs5435未满足Hardy-Weinberg平衡条件,予以剔除。校正性别、年龄、高血压、糖尿病、吸烟史、总胆固醇、甘油三酯、心率和体质指数后,rs16956647基因型与冠心病存在明显关联[加性模型:P=0.016,OR=0.80(95%CI=0.67~0.96);显性模型:P=0.002,OR=0.71(95%CI=0.57~0.89)]。进一步按是否患糖尿病分层后进行基因型关联分析,结果显示仅在糖尿病组rs16956647位点与冠心病呈显著关联[加性模型:P=0.048,OR=0.82(95%CI=0.67~0.99);显性模型:P=0.007,OR=0.72(95%CI=0.56~0.91)]。结论在中国广东汉族人群中,GLUT4基因多态性与冠心病易感性之间的关联可能与患者胰岛素抵抗有关。     

脑钠肽基因多态性与先天性心脏病易感性的相关性研究

目的研究博罗地区人群中脑钠肽(NPPB)基因的SNP位点(rs198389和rs198388)与先天性心脏病易感性的相关性。方法利用多重SNa Pshot技术,检测30例先天性心脏病患者和30例正常对照NPPB基因SNP位点(rs198389和rs198388)的基因型,评价NPPB基因多态性位点与先天性心脏病遗传易感性的相关性。结果 NPPB基因rs198389位点3种基因型(AA、AG和GG)分布频率在CHD病例组中分别为43.3%、36.7%和20.0%,与对照组相比差异有统计学意义(p<0.05),AG基因型和GG基因型均能增加先天性心脏病的发病风险(OR=3.76,95%CI=2.14~5.02;OR=2.25,95%CI=1.05~3.34);NPPB基因rs198388位点的基因型(AA和GG)分布频率在CHD病例组中分别为20.0%和63.3%,与对照组相比差异有统计学意义(p<0.05),GG基因型能增加先天性心脏病的发病风险(OR=5.68,95%CI=4.86~7.05)。结论博罗地区人群中,脑钠肽(NPPB)基因的SNP位点(rs198389和rs198388)与先天性心脏病的遗传易感性相关。     

HLA-DQ基因遗传变异与丙型肝炎病毒感染转归的相关性研究

目的 探讨遗人类白细胞抗原（human leukocyte antigen,HLA）DQ基因多态性与丙型肝炎感染转归的关联。方法 应用TaqMan探针方法检测339例丙型肝炎病毒（hepatitis C virus,HCV）持续感染者,262例HCV自限感染者和942例健康对照者HLA-DQ基因rs2856718和rs7453920位点的基因多态性,比较不同基因型与丙型肝炎病毒感染转归的关系。结果 采用多因素Logistic回归分析,结果显示rs2856718位点杂合基因型AG在感染组中的频率均低于对照组（调整OR=0.73,95%CI:0.56~0.94）;另外,rs7453920 AA基因型可增加个体对HCV的易感性（调整OR=1.75,95%CI:1.01~3.03）。结果显示,与AG单倍型相比,携带AA单倍型的个体可增加丙型肝炎易感性（调整OR=1.67,95%CI:1.11~2.52）。分层分析结果发现,在男性人群中,rs2856718位点的杂合基因型AG在感染组中的频率低于对照组（调整OR=0.68,95%CI:0.51~0.93）;在45~60岁人群中,rs7453920位点突变纯合基因型GG在感染组中的频率高于对照组（调整OR=2.35,95%CI:1.11~4.98）。结论 HLA-DQ基因多态性与丙型肝炎病毒感染转归存在关联。     

SMAD4基因多态性与煤工尘肺易感性

目的 探讨SMAD4基因单核苷酸多态性(SNPs)与煤工尘肺易感性的关系.方法 采用病例-对照的研究方法,选择438例煤工尘肺患者为病例组,448例同单位、同工种、工龄接近、无尘肺的煤尘接触者为对照组,进行统一的问卷调查;拍摄高仟伏X线后前位胸片;采集外周静脉血,酚-氯仿法提取DNA;根据中国人群HapMap database数据库查找SNP位点,多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测SMAD4 6个SNPs位点的基因型.结果 6个SNPs位点的基因型分布频率中,仅SMAD4(rs10502913)病例组和对照组各基因型分布频率比较,差异有统计学意义(x2=6.512,P=0.038).携带SMAD4(rs10502913)AA基因型者发生煤工尘肺的危险性明显增高(调整后OR=1.63,95%CI=1.00～2.69,P=0.05);以是否吸烟为分层分析显示,携带SMAD4(rs10502913)AG基因型的不吸烟者发生煤工尘肺的危险性降低(调整后OR=0.54,95%CI=0.37～0.78,P＜0.01),而携带SMAD4(rs10502913)AG、AA基因型的吸烟者发生煤工尘肺危险性均增高(AG调整后OR=1.59,95%CI=1.01～2.50,P＜0.05;AA调整后OR=2.28,95%CI=1.09～4.80,P＜0.05);以煤工尘肺分期为分层分析显示,Ⅰ期尘肺组携带SMAD4(rs10502913)AA基因型者发生尘肺的危险性是携带GG型的2.42倍(调整后OR=2.42,95%CI=1.41～4.14,P＜0.01).携带SMAD4(rs9304407)GG基因型者煤工尘肺患病危险性与CC基因型比较明显降低(调整后OR=0.65,95%CI=0.43～0.98,P＜0.05);以是否吸烟为分层分析显示,不吸烟携带SMAD4(rs9304407)GC、GG基因型者发生煤工尘肺危险性明显降低(GC基因型调整后OR=0.60,95%CI=0.36～1.00,P＜0.05;GG基因型调整后OR=0.43,95%CI=0.25～0.74,P＜0.01).结论 SMAD4(rs10502913)位点AA基因型增加了煤工尘肺的危险性,SMAD4(rs9304407)位点GG基因型可能在尘肺的发生发展中起保护性作用.     

着色性干皮病基因多态性及单体型与肺癌遗传易感的关联

目的探讨DNA的修复基因着色性干皮病基因B(XPB)、XPD、XPG的单核苷酸多态性和单体型与肺癌遗传易感的关联。方法用病例-对照研究的方法,选择海南省有吸烟暴露史、诊断明确的肺癌患者100例为病例组,与其有相近吸烟暴露史、胸外科其他疾病(如胸外伤、支气管扩张、肺结核等)患者100例为对照组。采用质谱法检测XPB基因rs4150441和rs4150434,XPD基因rs171140和rs11878544,XPG基因rs4771436、rs2094258、rs17655位点的多态性,采用Halopview软件进行单体型构建,探讨XP基因多态性及单体型与肺癌遗传易感性的关联。结果 XPB基因的rs4150434位点,携带GA基因型个体患肺癌的易感性是携带GG基因型个体的2. 071倍(OR=2. 071,95%CI 1. 055～4. 067),携带AA基因型个体患肺癌的易感性是携带GG基因型个体的2. 535倍(OR=2. 535,95%CI 1. 063～6. 044)。XPG基因的rs4771436位点,携带GG基因型个体患肺癌的风险是携带TT基因型个体的2. 494倍(OR=2. 494,95%CI 1. 038～5. 992)。XPG基因的rs2094258位点,携带AA基因型个体对肺癌的易感性是携带GG基因型个体的3. 020倍(OR=3. 020,95%CI1. 015～8. 980)。单体型结果显示,XPB基因rs4150441位点(G> A)和XPB rs4150434位点(G>A)所构成的单体型中,GA单体型的肺癌易感性是GG单体型的3. 643倍(OR=3. 643,95%CI 1. 113～11. 921)。XPG基因rs2094258位点(G>A)、rs4771436位点(T>G)和rs17655位点(C>G)所构成的单体型中,ATC单体型的肺癌易感性是GTC单体型的3. 800倍(OR=3. 800,95%CI 1. 073～13. 459)。结论XPB rs4150434、XPG rs4771436、XPG rs2094258位点多态性与肺癌的遗传易感性相关联,XPB基因的GA单体型和XPG基因的ATC单体型可能增加肺癌的发病风险。     

HLA-DQ基因多态性与汉族人群丙型肝炎感染转归的相关性研究

目的探讨人类白细胞抗原(Human leukocyte antigen,HLA)DQ基因多态性与汉族人群丙型肝炎病毒(HCV)感染转归的关联。方法应用TaqMan探针方法,在江苏地区HCV高危人群中检测339例持续感染者、262例自限感染者和942例健康对照者的HLA-DQ基因rs2856718和rs7453920位点的基因多态性,分析不同基因型与HCV感染转归的关系。结果多因素logistic回归分析结果显示,rs2856718位点杂合基因型AG在感染组中的频率均低于对照组(调整OR=0.73,95%CI:0.56~0.94);单倍型分析显示,与AG单倍型相比,携带AA单倍型的个体可增加丙型肝炎易感性(调整OR=1.67,95%CI:1.11~2.52)。结论 HLA-DQ基因多态性与汉族人群丙型肝炎病毒感染转归存在关联。     

TERT基因rs2736100位点多态性与中国人群肺癌易感性关联的Meta分析

目的探讨TERT基因rs2736100位点多态性与中国人群肺癌易感性的关联。方法检索PubMed、CNKI、万方、维普等数据库,收集以中国人群为研究对象的关于rs2736100位点多态性与肺癌易感性关联的文献,用RevMan 5.0软件进行Meta分析,并评估文献的发表偏倚。结果最终纳入12篇文献,累计病例组8 651例,对照组11 484例。Meta分析结果显示,rs2736100位点的等位基因模型(G vs T)增加了肺癌的易感性[OR=1.23,95%CI:1.18～1.28,P0.01]。进一步根据基因分型进行分层研究,结果表明显性基因模型(GG+GT vs TT)[OR=1.31,95%CI:1.24～1.40,P0.01]、隐性基因模型(GG vs GT+TT)[OR=1.30,95%CI:1.21～1.40,P0.01]、共显性基因模型(GG vs TT)[OR=1.50,95%CI:1.38～1.63,P0.01和共显性基因模型(GT vs TT)[OR=1.26,95%CI:1.18～1.35,P0.01]均增加了肺癌的易感性。结论 TERT基因上的rs2736100位点多态性与中国人群肺癌的易感性密切相关,携带有rs2736100-G等位基因的基因型增加了肺癌的发病风险。     

转化生长因子β1基因多态性与哮喘易感性Meta分析

目的探讨转化生长因子-β1(TGF-β1)基因多态性与哮喘易感性之间的关联。方法检索Pubmed、Embase、Medline、Scopus、CBM、中国知网、万方和维普等数据库,收集国内外关于研究TGF-β1基因多态性与哮喘易感性关联的文献,采用Stata 12.0软件对符合纳入标准的文献进行Meta分析。结果 TGF-β1基因C-509T位点纳入文献19篇,包括4 938例哮喘病例和5 838例对照,T869C位点文献7篇,包括1 327病例和1 258例对照。Meta分析结果显示,TGF-β1基因C-509T位点多态性与哮喘易感性有关[(Tvs.C):P=0.010,OR=1.17,95%CI=1.04~1.31;(TT+CT vs.CC):P0.01,OR=1.34,95%CI=1.14~1.57;(TT vs.CC):P=0.001,OR=1.42,95%CI=1.15~1.76]。TGF-β1基因T869C位点多态性在总人群中与哮喘无关,经过亚组分析表明,在成年人群中发现多态性和哮喘存在统计学关联[(C vs.T):P=0.020,OR=1.19,95%CI=1.03~1.37;(CC vs.CT+TT):P=0.032,OR=1.31,95%CI=1.02~1.69;(CCvs.TT):P=0.029,OR=1.39,95%CI=1.03~1.88],但是在儿童人群中未发现多态性和哮喘存在统计学关联;在亚洲人群和高加索人群中均未发现多态性和哮喘存在统计学关联。结论 TGF-β1基因C-509T位点多态性与哮喘易感性有关,携带T等位基因可能增加哮喘患病风险;TGF-β1基因T869C位点只与成人哮喘有关,提示其在哮喘遗传易感性中可能起到附加效应。     

Construction of a novel vaccine by conjugating a B-cell epitope of DPP4 to peptide IA2(5)-P2-1 to significantly control type 1 diabetes in NOD mice

Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing β cells leads to impaired glucose metabolism and its attendant complications. IA2(5)P2-1, a potent immunogenic carrier which designed by our laboratory, can induce high titer specific antibodies when carry a B cell epitope, such as B cell epitopes of DPP4, xanthine oxidase, and Urate transporter protein. In this report, we describe a novel multi-epitope vaccine composing a peptide of DPP4, an anti-diabetic B epitope of Insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60). Immunization with the multi-epitope vaccine in non-obese diabetic (NOD) mice successfully induced specific anti-DPP4 antibody, inhibited plasma DPP4 activity, and increased serum GLP-1 level. Moreover, this antibody titer was correlated with the dose of immunization (20μg, 100μg). Inoculation of this vaccine in NOD mice significantly control blood glucose level, improved glucose excursion and increased insulin level in vivo. Consistent with a lower diabetic and insulitis incidence, a induced splenic T cells proliferation and tolerance were observed. IFN-γ secretion reduced and IL-10 increased significantly in the D41-IA2(5)-P2-1 treated mice compared to P277 and control group due to the potential immunomodulatory effect of the epitope in the vaccine. Immunohistochemical analysis and cytometry showed a rebalance of Th1/Th2 in NOD mice. Our results demonstrate that this multi-epitope vaccine may serve as a promising therapeutic approach for type 1 diabetes.     

Induction of mucosal and systemic immunity against respiratory syncytial virus by inactivated virus supplemented with TLR9 and NOD2 ligands

Respiratory syncytial virus (RSV) infection is the most important viral cause of severe respiratory disease in infants and children worldwide and also forms a serious threat in the elderly. The development of RSV vaccine, however, has been hampered by the disastrous outcome of an earlier trial using an inactivated and parenterally administered RSV vaccine which did not confer protection but rather primed for enhanced disease upon natural infection. Mucosal administration does not seem to prime for enhanced disease, but non-replicating RSV antigen does not induce a strong mucosal immune response. We therefore investigated if mucosal immunization with inactivated RSV supplemented with innate receptor ligands, TLR9 (CpG ODN) and NOD2 (L18-MDP) through the upper or total respiratory tract is an effective and safe approach to induce RSV-specific immunity. Our data show that beta-propiolactone (BPL) inactivated RSV (BPL-RSV) supplemented with CpG ODN and L18-MDP potentiates activation of antigen-presenting cells (APC) in vitro, as demonstrated by NF-κB induction in a model APC cell line. In vivo, BPL-RSV supplemented with CpG ODN/L18-MDP ligands induces local IgA responses and augments Th1-signature IgG2a subtype responses after total respiratory tract (TRT), but less efficient after upper respiratory tract (intranasal, IN) immunization. Addition of TLR9/NOD2 ligands to the inactivated RSV also promoted affinity maturation of RSV-specific IgG antibodies and shifted T cell responses from mainly IL-5-secreting cells to predominantly IFN-γ-producing cells, indicating a Th1-skewed response. This effect was seen for both IN and TRT immunization. Finally, BPL-RSV supplemented with TLR9/NOD2 ligands significantly improved the protection efficacy against a challenge with infectious virus, without stimulating enhanced disease as evidenced by lack of eotaxin mRNA expression and eosinophil infiltration in the lung.We conclude that mucosal immunization with inactivated RSV antigen supplemented with TLR9/NOD2 ligands is a promising approach to induce effective RSV-specific immunity without priming for enhanced disease.     

胃癌易感基因筛选及多基因危险度分析

[目的]探讨我国汉族人群胃癌患者遗传易感基因,并进行多基因危险度分析。[方法]采用1：1配对病例对照研究方法,收集南京市汉族人群原发性胃癌患者585例和相应非肿瘤及非消化道疾病患者为研究对象,应用限制性片段长度多态性聚合酶链反应（PCR-RFLP）和基因特异性聚合酶链反应（AS-PCR）技术分析CYP2E1、GSTM1、GSTT1、NAT2、ALDH2、MTHFR、XRCC1、IL-1β、VDR、TNF等基因型别;以条件logistic回归模型对基因及基因间的交互作用进行分析,选出易感基因,多基因联合作用危险度分析统计模型对选出的危险因素进行多基因危险度评价。[结果]原发性胃癌遗传易感因素有8项,分别是CYP2E1（c1／c1）、NAT2表型（慢乙酰化型）、MTHFRA1298C（A／C）、IL-1β（C/T）、NAT2M2（A／A）、XRCC1194（T／T）、NAT2M1（T/T）、VDR TaqI（T/T）。利用多基因联合作用危险度分析模型对多基因危险度评价分析,可以更直观地发现多基因组合的OR值与其基因频率存在高度相关性,即随易感基因的增加,易感基因组合危险度分布曲线会向更加危险的方向移动。并呈现一定的量化关系。[结论]通过对筛选出的易感基因进行多基因危险度分析,可更有效地推进对汉族人群中胃癌的高危人群识别及对其采取预防和干预措施。     

HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 inducing anti-inflammatory immune response in NOD mice by nasal administration

Mucosal administration of autoantigen HSP65 can induce anti-inflammatory immune response and decrease organ-specific inflammation and disease in several models of autoimmunity, such as arthritis and atherosclerosis. We have been interested in whether the HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 can also induce anti-inflammatory immune response in NOD mice by mucosal administration. Thus, the dual functions of anti-type 1 diabetes of HSP65 and P277 will be obtained. To test this hypothesis, we examined the effect of intranasal vaccination with P277 tandem repeat sequences carried by HSP65 in the absence of adjuvants on autoimmune diabetes in NOD mice. We found a significant decrease in the incidence of diabetes, inhibition of insulitis, reduction in IgG2a isotype antibodies to P277 and proinflammatory cytokines IFN-γ and IL-2 secretion, increased IgG1, IgG2b subclass antibodies to P277 and anti-inflammatory cytokines IL-10 and IL-4 secretion, and reduced proliferation in nasal administration of the fusion protein HSP65-6 × P277. Our results demonstrate that HSP65 may serve as a particularly advantageous carrier for P277-based vaccines and mucosal administration may be a therapeutic approach for treatment of type 1 diabetes.     

胃癌的环境与遗传危险因素及归因危险度分析

目的分析胃癌的环境与遗传危险因素并进行归因危险度评价。方法采用病例对照研究方法．对南京地区121例原发性胃癌病例进行环境危险因素调查，并对相关酶系基因多态性进行分析．综合评价环境危险因素及遗传危险性在胃癌发生中的归因危险度。结果在南京地区人群中，吸烟、食用腌制食品等两种环境危险因素与遗传危险因子细胞色素氧化酶P4502E1(CYP2E1)和N-乙酰化酶(NAT2)的基因型的人群综合归因危险度达69．7％。胃癌的发生主要是环境危险因素与内在遗传持点共同作用的结果。结论对胃癌的干预应同时考虑环境危险因素和遗传危险性，在了解个体遗传易感性的基础上，对其相应的环境危险因素进行干预，以达到Ⅰ级预防的目的。     

Mycobacterium indicus pranii mediates macrophage activation through TLR2 and NOD2 in a MyD88 dependent manner

Mycobacterium indicus pranii (MIP) is a non-pathogenic strain of mycobacterium and has been used as a vaccine against tuberculosis and leprosy. Here, we investigated the role of different pattern recognition receptors in the recognition of heat-killed MIP by macrophages. Treatment of macrophages with MIP caused upregulation of pro-inflammatory cytokines (like TNFα and IL-1β) which was mediated through both TLR2 and NOD2, as revealed by our knockdown and/or knockout studies. Mechanistically, MIP-induced macrophage activation was shown to result in NF-κB activation and drastically abrogated by MyD88 deficiency, suggesting its regulation via an MyD88-dependent, NF-κB pathway. Interestingly, the IFN-inducible cytokine, CXCL10, which is known target of the TRIF-dependent TLR pathway was found to be upregulated in response to MIP but, in an MyD88-dependent manner. Collectively, these results demonstrate macrophages to recognize and respond to MIP through a TLR2, NOD2 and an MyD88-dependent pathway. However, further studies should clarify whether additional TLR-dependent or -independent pathways also exist in regulating the full spectrum of MIP action on macrophage activation.     

回族人群饮食习惯与胃癌发生的相关性研究

目的研究回族人群独特的饮食习惯与胃癌患病的相关性,并进一步探讨与回族人群胃癌发病相关的饮食危险因素。方法采用1︰1配对的病例对照研究方法,问卷调查126例胃癌和贲门癌回族患者以及126例非病例回族人群的饮食习惯,采用单因素和多因素条件Logistic回归模型进行数据分析。结果经单因素与多因素条件Logistic回归分析结果显示,三餐不定时、常食腌制食品、常食油炸食品均有统计学意义(P﹤0.05,OR值分别为3.054,2.363,1.915)。常食水果可降低胃癌的发生(OR=0.281,P﹤0.01)。结论三餐不定时、常食腌制食品及常食油炸食品可能会增加回族人群胃癌患病的危险性,而多食水果是回族胃癌的保护因素。     

Incidence of Crohn’s disease and CARD15 mutation in a small township in Sicily

Background:  The incidence of Crohn’s disease (CD) has been shown to be lower in Southern than in Northern Europe. Data on the frequency of the NOD2/CARD15 mutations for Mediterranean area are very scant. Aim:  To determine the incidence of CD from 1979 to 2002 in a township in Sicily together with the allele frequency of NOD2/CARD15 mutations in patients, family members and controls, and to determine the allele frequency of these mutations in sporadic CD from other areas of Sicily in comparison with a control population. Methods:  Casteltermini is a small town close to Agrigento (Sicily) with a population of 9,130 inhabitants. All the diagnoses of inflammatory bowel disease (IBD) made from 1979 to 2002 were obtained through the local health authority. NOD2/CARD15 mutations were studied in 23 out of the 29 patients with CD in Casteltermini, in 60 family members and in 64 controls. NOD2/CARD15 was also studied in 80 sporadic cases of CD disease among Sicilians outside Casteltermini and 118 healthy controls. Results:  From 1979 to 2002, 29 patients with CD and 13 patients with ulcerative colitis (UC) were registered. The 6-year mean incidence of CD ranged from 8.0 to 17 new cases for every 100,000 inhabitants, whereas the mean incidence of UC ranged from five new cases to 7.8 for every 100,000 inhabitants. The allele frequencies of NOD2/CARD15 mutations (L1007finsC, G908R, R702W) were 8.7, 4.3 and 8.7%, respectively, in CD cases; 5.0, 4.2 and 3.1% in family members; 1.6, 2.3 and 3.1% in controls. In sporadic Sicilian CD patients outside Casteltermini the allele frequency was 7.5, 8.1, 6.2% whereas in control population it was 3.3, 1.6, 1.6%. Conclusions:  A high incidence of CD compared with UC was observed in this small town in Southern Italy. The frequency of NOD2/CARD15 mutations in CD is similar to other Caucasian population studied so far.     

Vitamin D Reduces Colitis- and Inflammation-Associated Colorectal Cancer in Mice Independent of NOD2

Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal cancer (CRC). Vitamin D (vD) induces NOD2 gene expression, enhancing immunity, while deficiency impairs intestinal epithelial integrity, increasing inflammation. This study investigated the effect of vD on CRC in colitis, and if preventive benefits are mediated via NOD2. Inflammation-associated CRC was induced by treating C57BL/6J and Nod2^?/? mice with azoxymethane (AOM) and dextran sodium sulfate (DSS) cycles (×3). vD-deficient mice displayed more severe colitis compared to vD-supplemented mice, with greater weight loss, higher colitis activity index, increased colonic weight/length ratios, and lower survival rates. Increased histological inflammation score and increased IL-6 were observed in the mucosa of vD-deficient mice. Overall incidence of colonic tumors was not significantly different between vD-deficient and vD-supplemented mice. Higher tumor multiplicity was observed in vD-deficient vs vD-supplemented groups (both mouse strains). After AOM/DSS treatment, decreased plasma 25(OH)D₃ levels and downregulation of vD target genes Cyp24 and Vdr were observed in both mice strains (vD-deficient or vD-supplemented diet), compared to saline-treated controls on the vD-deficient diet. In conclusion, vD supplementation reduced colitis severity and decreased the number of inflammation-associated colorectal tumors in both C57BL/6J and Nod2^?/? mice, independent of NOD2.