Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma

The aim of the study was to investigate whether interleukin-10 (IL-10) genetic polymorphisms influence this cytokine production as well as the incidence and outcome of diffuse large B-cell lymphoma (DLBCL). The frequency of IL-10(-1082G) allele was found to be higher in 199 patients with DLBCL as compared with 112 control subjects (0.47 versus 0.39, P =.043). Increased serum levels of IL-10 were associated with adverse prognostic factors and poor DLBCL outcome. The frequencies of IL-10(-819T) and IL-10(-592A) alleles were lower in patients with elevated IL-10 serum levels (0.155 versus 0.32, P =.14). As compared with patients carrying the IL-10(-1082AA) genotype, patients with the IL-10(-1082G) allele (IL-10(-1082GG/GA) genotypes) had higher complete remission rate (78% [confidence interval (CI), 71%-85%] versus 65% [CI, 52%-78%], P =.07), 5-year freedom from progression (FFP) (60% [CI, 52%-68%] versus 40% [CI, 27%-53%], P =.013), and overall survival (OS) (63% [CI, 55%-71%] versus 33% [CI, 20%-45%], P =.0009). Among factors of the International Prognostic Index, IL-10(-1082G) allele remained an independent variable, predicting longer freedom from progression (FFP) (RR [relative risk] =.76, P =.00035) and OS (RR =.78, P =.0015). These results indicate that IL-10 production contributes to the clinical course of DLBCL and that this phenomenon involves a substantial genetic component.     

腹泻型肠易激综合征患者中IL-10基因多态性的研究

目的 探讨腹泻型肠易激综合征（D-IBS）与IL-10基因启动子区域-1082、-819和-592位点单核苷酸多态性之间的关系。方法用扩增受阻突变系统-PCR方法对41例健康对照和43例D-IBS患者IL-10基因启动子区域-1082、-819和-592位点单核苷酸多态性进行研究。结果 -819位点D-IBS患者T／T基因型频率显著高于健康对照组（67．4％比39．0％,P〈0．05）,C／T和C／C基因型频率虽较对照组低（分别为23．3％比43．9％和9．3％比17．1％）,但差异无统计学意义（P〉0．05）;-0592位点D-IBS患者A／A基因型频率显著高于对照组（67．4％比39．0％,P〈0．05）,C／A和C／C基因型频率均较对照组低（分别为23．3％比43．9％和9．3％比17．1％）,但差异无统计学意义（P〉0．05）;-1082位点基因型频率差异无统计学意义（P〉0．05）。IL-10启动子-819位点T等位基因频率在D-IBS患者显著高于健康对照组（79．1％比61．0％,P〈0．05）,C等位基因频率在D-IBS患者显著低于健康对照组（20．9％比39．0％,P〈0．05）;-592位点A等位基因频率在D-IBS患者显著高于对照组（79．1％比61．0％,P〈0．05）,C等位基因频率在D-IBS患者显著低于对照组（20．9％比39．0％,P〈0．05）;-1082位点G或A等位基因频率在D-IBS患者与对照组间差异无统计学意义。结论IL-10基因启动子区域一819T／T和-592A／A基因型可能与D-IBS发生有关。     

IL-10基因多态性与乙肝肝硬化易感性的相关性研究

探讨白细胞介素10(IL-10)基因多态性与乙型肝炎肝硬化易感性的关系.采用聚合酶链反应-限制性片段长度多态性(PCR-PFLP)分析方法,检测100例乙肝肝硬化患者及124例健康对照组IL-10基因启动子-1082G/A、-592A/C位点的基因多态性,并确定了其基因型和等位基因频率的分布.肝硬化组与对照组IL-10基因启动子-592A/C位点基因型分布频率和等位基因频率差异无显著性(P＞0.1),肝硬化组-1082G/A位点AA基因型频率及A等位基因频率高于对照组(P＜0.05),G等位基因相对于A等位基因患肝硬化的机会比为0.373(95%CI:0.166～0.838).IL-10基因多态性与肝硬化易感性相关,基因启动子-1082G/A位点AA基因型携带者肝硬化易感性高.     

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.     

Interleukin-10 Promoter and the CCR5 Polymorphisms in Iranian Azari Population with Multiple Sclerosis

Background: Changes in the expression of cytokines as the result of the single nucleotide polymorphisms (SNPs), can affect the incidence of multiple sclerosis (MS). Objective: To investigate the relationship between the frequencies of interleukin-10 (IL-10)-1082 A/G (rs1800896) and CCR5-delta32 genotypes and susceptibility to MS in the Iranian Azari population. Methods: IL-10-1082 A/G SNP and the CCR5-delta32 were genotyped in 152 patients suffering from MS and 242 healthy non-relatives by allele specific-PCR and simple PCR methods, respectively. Results: The frequencies of AA (37.6%) and AG (55.9%) genotypes of IL-10-1082 were significantly high in the control (p = 0.021) and MS patients (p = 0.015), respectively, with no statistical difference between these groups. There was no significant difference in the CCR5 gene based on the possession of wild/wild and wild/del32 genotypes between MS patients and the control group. The del32/del32 genotype was not seen in any of the investigated groups. Tobacco (cigarettes and hookahs) consumption was higher among the MS patients (p=0.004), and this has the potential to raise the risk of MS in both the individuals and their family. However, it had no significant relation with the frequency of different genotypes of the IL-10-1082 and the CCR5. Conclusion: Our finding conclude on possible role of AA genotype of IL-10 -1082 as a protective factor in MS.     

Human leukocyte antigen class II alleles may contribute to the severity of hepatitis C virus-related liver disease

To investigate whether genetic differences in cytokine promoter polymorphisms effect various outcomes after exposure to Epstein-Barr virus (EBV) infection, 30 patients with EBV-positive gastric carcinoma (GC), 120 patients with EBV-negative GC, and 220 control subjects were enrolled. Promoter polymorphisms of tumor necrosis factor (TNF)-alpha at positions -238 and -308 and of interleukin (IL)-10 at position -1082 were determined. The frequency of the high-producer allele (-308A) in the TNF-alpha gene was significantly higher among EBV-positive GC patients compared with control subjects (23.3% vs. 12.0%, P<.05), whereas the frequency of the high-producer allele (-1082G) in the IL-10 gene was significantly higher among EBV-negative GC patients compared with control subjects (6.3% vs. 3.0%, P<.05). These data support the notion that genetic factors may modify the outcomes of infectious diseases through different TNF-alpha- or IL-10-producing capabilities.     

Interleukin-10 - 1082 GG polymorphism influences the occurrence and the clinical characteristics of hepatitis C virus infection

BACKGROUND/AIMS: In this study, we determined the genotypic and allelic frequencies of the Interleukin (IL)-10(-1082G/A) IL-10(-592A/C), and IL-10(-819C/T) polymorphisms, and their association with the risk to develop B cell Non Hodgkin Lymphoma (NHL) in hepatitis virus C (HCV) carriers. RESULTS: Genetic polymorphisms in the IL-10 gene promoter were studied in 250 consecutive patients with B-cell NHL with no clinical and/or laboratory findings of cryoglobulinemia, 142 NHL/HCV- and 108 NHL/HCV+ with chronic hepatitis (CH), 120 consecutive subjects with HCV-related CH, and 110 age, sex-matched healthy blood donors. The frequency of the IL-10(-1082GG) genotype vs remaining genotypes (IL-10(-1082GA/AA)) was higher in NHL/HCV+ patients than HCV-related CH patients (P=0.0002, OR=2.89, CI: 1.62-5.15) and in NHL/HCV+ than NHL/HCV- patients (P=0.0001, OR=2.99, CI: 1.72-5.19). Moreover, the IL-10(-1082GG) genotype was more prevalent in indolent NHL/HCV+ cases than aggressive NHL/HCV+ (P=0.0004, OR=4.97, CI: 2.10-11.79). Finally, we confirmed that IL-10(-1082GG) genotype is associated with higher IL-10 production compared to AA homozygous (P=0.037). CONCLUSIONS: The high IL-10 production, due to IL-10(-1082GG) genotype, influences the clinical expression of the HCV infection by increasing susceptibility to develop NHL and might contribute to the indolent form of the disease.     

Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients

OBJECTIVES: We asked if single nucleotide polymorphisms (SNP) in inflammatory cytokine genes related to 3-year survival in ill elderly subjects and if genotypes differed between the elderly and a younger control population. DESIGN: Prospective observational study. SETTING: Two geriatric departments at a university hospital. SUBJECTS: Eighty three acutely admitted geriatric patients (83 +/- 7 year, 70% women) and 207 young healthy subjects (40 +/- 1 year, 37% women) were included. OUTCOME MEASURES: Single nucleotide polymorphisms in the genes of tumour necrosis factor (TNF)-alpha-308 G/A, interleukin (IL)-1beta-511 C/T, IL-6-174 G/C and IL-10-1082 A/G were analysed. In the geriatric patients SNP in lymphotoxin (LT)-alpha +252 G/A and serum levels of TNF-alpha, IL-6, IL-10, soluble IL-I receptor(R)II were also determined, as well as the 3-year mortality. RESULTS: The allele distribution did not differ significantly between the elderly and the young. In the female elderly, 3-year survival was doubled (P < 0.05) in those with the high-producing genotypes of IL-6 -174 GG and TNF-alpha -308 GA compared with those with low-producing alleles. In contrast, men with high-producing LT-alpha +252 AA and IL-1beta-511 CT&TT genotypes displayed halved 3-year survival (P < 0.05) compared with those with low-producing genotypes, whereas possession of the high-producing IL-10 -1082 GG genotype favoured survival. Serum IL-10 was higher in the high-producing IL-10 genotype in females. CONCLUSION: As high-producing IL-6 -174 genotype favoured 3-year survival in women, whereas the likewise high-producing LT-alpha +252 and IL-1beta -511 genotypes were associated with poor survival in men, we conclude that the specific genotypes, in association with gender, may act as determinants for survival in elderly patients.     

Interleukin-10 polymorphisms in Spanish patients with IBD

BACKGROUND: Inflammatory bowel disease (IBD) is considered a heterogeneous, complex polygenic disease where both genetic and environmental factors are involved in the development of the disease. Interleukin-10 (IL-10) is a regulatory cytokine that might play an important role in disease pathogenesis. IL-10 contains single nucleotide polymorphisms and 2 polymorphic microsatellites in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers is associated with IBD among Spanish patients. METHODS: We genotyped 470 patients with IBD, 242 with ulcerative colitis and 228 with Crohn's disease (CD), and 572 ethnically matched controls for microsatellites IL-10R and IL-10G and 2 single nucleotide polymorphisms at positions -1082 and -819 in the proximal promoter of the gene. RESULTS: IL-10G14 microsatellite allele as well as -1082G allele were significantly increased in patients with CD. The combined presence of both alleles in 1 individual notably increased the risk to develop CD (P = 0.00006, odds ratio = 3.18). CONCLUSION: IL-10 polymorphisms contribute to susceptibility to CD in Spanish population.     

Tumor necrosis factor-alpha and Interleukin-10 gene promoter polymorphisms in Turkish rheumatoid arthritis patients

Tumor necrosis factor and interleukin 10 have been implicated in the pathogenesis of rheumatoid arthritis (RA). Certain single-nucleotide polymorphisms (SNPs) within the promoter region of the IL-10 and TNF genes have been associated with altered levels of circulating IL10 and TNF. We aimed to explore the association of IL-10 and TNF-alpha polymorphisms in Turkish RA patients. We analyzed the association of TNF-alpha (-308G/A, -238G/A, -376G/A) and IL10 (-1082G/A, -819C/T, -592C/A) polymorphisms in 98 Turkish patients with rheumatoid arthritis and 122 healthy subjects using ARMS-PCR. The correlation of these findings with RF positivity and erosive disease in RA patients was also sought. A significant association was found between having RA and -1082 G allele (p = 0.008; OR = 1.44, 95% CI 1.11-1.86). There was no association between RA and -819C/T polymorphism. Significant differences were observed in IL10 GCC and ACC haplotypes distribution between RA and control subjects (p = 0.006; OR = 1.46, 95% CI 1.13-1.89 and p = 0.011; OR = 1.43, 95% CI 1.09-1.88, respectively). No statistically significant association was found between TNF-alpha 308G/A, -238G/A, -376G/A polymorphisms and RA. No significant association was found between RF positivity and erosive disease and TNF-alpha, IL10 gene polymorphisms. In addition, when combined genotypes were analyzed, no significant difference was found between RA patients and healthy controls. Our findings suggest that IL-10 1082 G/A polymorphism or GCC, ACC haplotypes may be associated with RA in Turkish patients.     

Polymorphisms in the interleukin-10 gene and relation to phenotype in patients with ulcerative colitis.

BACKGROUND AND OBJECTIVES: Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation in inflammatory bowel disease. In our population of Spanish ulcerative colitis (UC) patients, we have previously demonstrated that two polymorphisms (IL-10.G14 microsatellite allele and homozygous for the -1082G allele (guanine at position -1082)) in the IL-10 gene were susceptibility markers for disease. No data exist regarding the relationship of these IL-10 polymorphisms with phenotypic subpopulations in UC. Therefore, this study sought to examine the contribution of IL-10 polymorphisms to phenotypical variability in UC. MATERIAL AND METHODS: A cohort of 215 Spanish unrelated patients with UC recruited in a single center was studied. All patients were rigorously phenotyped and followed for at least 3 years (mean time: 11.8 years). The clinical phenotype was established before genotyping. Genotyping was performed using polymerase chain reaction (PCR) assays. RESULTS: Patients with UC included 129 (60%) men and 89 (40%) women. Mean age at diagnosis was 38 years, with a range of 8-83. Disease extent included 127 (59.1%) left-side patients and 88 (40.9%) extensive patients. Neither UC phenotype variable was associated with the presence of susceptibility polymorphisms (10G14 microsatellite and -1082G allele). CONCLUSIONS: In Madrid's Spanish population of UC patients, the carrying of the ILG14 microsatellite or -1082G polymorphism in the IL-10 gene was not associated with phenotype of disease.     

白细胞介素-10和肿瘤坏死因子基因多态性与湖北汉族人群胃十二指肠疾病及幽门螺杆菌感染的相关性

目的 研究我同湖北汉族人群IL-10及TNF的基因多态性与胃十二指肠疾病及幽门螺杆菌(Hp)感染的关系.方法 采用病例财照研究和聚合酶链反应.限制性片段长度多态性(PCR-RFLP)方法检测605例胃十二指肠疾病患者(包括196例慢性胃炎、189例胃十二指肠溃疡及220例胃癌患者)和624例健康对照者中IL-10基因启动子区3个位点(IL-10-1082/-819/-592)的等位基因型和TNFα-308、LTα(淋巴毒素α,亦称TNFβ)Nco Ⅰ、AspH Ⅰ双等位基因型分布;用ELISA法检测血清中Hp-IgG及cagA-IgG抗体水平.结果 (1)IL-10-1082 AG+GG基因型在胃癌组、慢性胃炎组及胃十二指肠溃疡组(非胃癌组)、健康对照组分布频率分别为20.0%、7.5%、6.0%和5.0%,IL-10-1082 AG+GG基因型分布在非胃痛组及健康对照组之间差异无统计学意义(P>0.05),而胃癌组高于非胃癌组(P<0.05)及健康对照组(P<0.05),其差异均有统计学意义.胃癌组中IL-10-592及-819两个位点与非胃癌组及健康对照组比较,基因型分布差异无统计学意义(P>0.05).IL-10-819位点与IL-10-592位点基因型分布频率一致.(2)胃癌组与其余3组比较,IL-10-1082 AG+GG基因型且Hp阳性的分布频率的差异有统计学意义(P<0.05).(3)LTα Nco Ⅰ AG基因型在Hp阳性胃癌患者中(66.7%)高于Hp阳性的健康对照组(47.8%),差异有统计学意义(P<0.05),该基因型与其他胃十二指肠疾病尤相关性.TNFα-308、LTα AspH Ⅰ与Hp感染及胃十二指肠疾病亦无相关性.结论 (1)IL-10-1082 AG+GG基因型与湖北地区汉族人群胃癌发生有相关性.(2)IL-10-1082 AG+GG基因型和LTα Nco Ⅰ AG基因型与湖北汉族人群Hp阳性胃癌有相关性.     

Effects of interleukin-10 gene polymorphism on the development of gastric cancer and peptic ulcer in Japanese subjects

BACKGROUND: Anti-inflammatory cytokines play an important role in downregulation of inflammation and the prevention of neoplastic disorders. Genetic variations of anti-inflammatory cytokines are assumed to influence such responses. The aim of the present study was to clarify the association between the IL-10 polymorphism, one of the representative anti-inflammatory cytokines, and susceptibility to gastric cancer and peptic ulcer in Japan. METHODS: The IL-10-1082 (A/G)/-819 (T/C)/-592 (A/C) polymorphisms were assessed in Helicobacter pylori-positive patients with gastritis only (n = 162), gastric ulcers (n = 110), duodenal ulcers (n = 94), or gastric cancers (n = 105), and H. pylori-negative controls (n = 168) by allele specific primer-polymerase chain reaction methods. RESULTS: The carriage of IL-10-592 C (age and sex-adjusted odds ratio [OR]: 1.851, 95% confidence interval [CI]: 1.018-3.380) and IL-10-819 C (adjusted OR: 1.868, 95%CI: 1.023-3.411) allele were associated with an increased risk for gastric cancer development, not gastric ulcer and duodenal ulcer. The IL-10-1082 polymorphism had no association with development of gastric cancer and peptic ulcers. The presence of the ATA/GCC haplotype of IL-10-1082/-819/-592 polymorphism significantly increased the risk of gastric cancer development (adjusted OR: 2.805, 95%CI: 1.258-6.254) compared with presence of the ATA/ATA haplotype. CONCLUSIONS: The IL-10-1082/-819/-592 genotype status and haplotype were associated with an increased risk for gastric cancer development, not peptic ulcer, in Japan. The genotyping test of this anti-inflammatory cytokine would be useful for the detection of individuals with higher risk of gastric cancer development.     

Association of interleukin 10 and interferon gamma gene polymorphisms with enterovirus 71 encephalitis in patients with hand, foot and mouth disease

Enterovirus 71 (EV71) is one of the common causative agents of hand, foot and mouth disease (HFMD), and is associated with several outbreaks with neurological complications including encephalitis. This study investigated the polymorphisms of interferon gamma (IFN-γ)+874 T/A and interleukin 10 (IL-10)-1082 G/A in 65 Chinese patients with EV71 encephalitis and 113 Chinese HFMD patients without complications. The polymorphisms of IFN-γ+874 T/A and IL-10-1082 G/A were determined by polymerase chain reaction (PCR)-amplification refractory mutation system (ARMS) and PCR-sequence-specific primer (SSP) analysis, respectively. The IFN-γ + 874 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (76.2%) compared with HFMD patients without complications (61.1%, p < 0.01). Similarly, the IL-10 - 1082 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (86.2%) compared with HFMD patients without complications (77.0%, p < 0.05). IFN-γ + 874 A and IL-10 - 1082 A alleles are associated with susceptibility to EV71 encephalitis in Chinese patients.     

Cytokine genotyping (TNF and IL-10) in patients with celiac disease and selective IgA deficiency

OBJECTIVE: Selective IgA deficiency (IgAD) and celiac disease (CD) are frequently associated and share the ancestral haplotype human leukocyte antigen (HLA)-8.1, which is characterized by a peculiar cytokine profile. The aim of this study was to evaluate the role of tumor necrosis factor (TNF) and interleukin (IL)-10 alleles in CD and CD-IgAD. METHODS: The distribution of some biallelic polymorphisms of both cytokine promoters (-308G-->A and -863C-->A at TNF promoter sequence and -1082G-->A, -819C-->A, and -592C-->T at IL-10 promoter) were typed using biotilinated specific probes in 32 celiac patients, in 34 CD-IgAD patients, and in 96 healthy controls. RESULTS: In CD and CD-IgAD, the -308A allele was significantly more frequent than in controls, whereas no significant differences were observed for the biallelic polymorphisms at the -863 and for the three IL-10 promoter polymorphisms. The evaluation of combined TNF and IL-10 genotypes showed in CD-IgAD a significant reduction of -308G/-1082G homozygous subjects and both in CD and CD-IgAD groups an increase of 308AA/1082GG. Accordingly, CD-IgAD patients positive both for -308A TNF and -1082A IL-10 showed an increase of TNF-alpha and a reduction of IL-10 serum levels. CONCLUSIONS: Genetically determined increased production of TNF-alpha and reduction of IL-10 may be relevant for susceptibility to CD, mainly in IgAD, as the different allele expression at TNF and IL-10 loci seems to influence cytokine production profile.     

Polymorphisms in interleukin-10 gene according to mutations of NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn＇s disease

AIM:To examine the contribution of interleukin-10(IL-10)gene polymorphisms to Crohn's disease(CD)phenotype,and the possible genetic epistasis betweenIL-10 gene polymorphisms and CARD15/NOD2 genemutations.METHODS:A cohort of 205 Spanish unrelated patientswith Crohn's disease recruited from a single centerwas studied.All patients were rigorously phenotypedand followed-up for at least 3 years(mean time,12.5years).The clinical phenotype was established prior togenotyping.RESULTS:The correlat on of genotype-Viennaclassification groups showed that the ileocolonic locationwas significantly associated with the-1082G allele in theNOD2/CARD15 mutation-positive patients(RR=1.52,95%CI,1.21 to 1.91,P=0.008).The multivariate analysisdemonstrated that the IL-10 G14 microsatellite allelein the NOD2/CARD15 mutation positive patients wasassociated with two risk factors,history of appendectomy(RR=2.15,95%CI=1.1-4.30,P=0.001)and smokinghabit at diagnosis(RR=1.29,95%CI=1.04-4.3,P=0.04).CONCLUSION:In Spanish population from Madrid,inCD patients carrying at least one NOD2/CARD15 mutation,the-1082G allele is associated with ileocolonic disease and the IL-10G14 microsatellite allele is associated withprevious history of appendectomy and smoking habit atdiagnosis.These data provide further molecular evidencefor a genetic basis of the clinical heterogeneity of CD.     

白细胞介素-10启动子-1082和-819位点基因多态性与肠易激综合征的关系

目的 探讨白细胞介素(IL)-10启动子区基因多态性与肠易激综合征(IBS)的关系.方法 采用聚合酶链式反应结合限制性片段长度多态性分析(PCR-RFLP),对313例IBS患者及281名对照者的1L-10启动子区-1082及-819位点进行基因型分析.结果 在-1082位点与-819位点,IBS组、对照组和总人数组中,各基因型的分布符合Hardy-Weinberg平衡规律.IL-10-819位点T等位基因频率腹泻型(79.8％)和混合型(77.1％)显著高于对照组(65.7％,P＜0.05).IL-10-1082位点A、G等位基因频率在各亚型与对照组间差异无统计学意义(P＞0.05),腹泻型与混合型间差异有统计学意义(P＜0.05).IBS组-819位点T/T基因型频率(51.1％)显著高于对照组(40.2％),C/T基因型显著低于对照组,差异均有统计学意义(P值均＜0.05);-819位点T/T基因型频率IBS的各亚型组显著高于对照组,C/T基因型IBS各亚型显著低于对照组,差异均有统计学意义(P值均＜0.05);C/C基因型在各亚型间差异无统计学意义(P＞0.05).-1082位点基因型在IBS组和对照组间的差异无统计学意义(P＞0.05);IBS腹泻型的-1082位点A/A基因型(93.3％)显著高于混合型IBS(82.4％),A/G基因型低于混合型IBS,差异均有统计学意义(P值均＜0.05);但IBS其他亚型间以及与对照组间差异无统计学意义(P＞0.05).结论 IL-10启动子区域-819位点T/T基因型可能与IBS发生有关,而-1082位点可能与IBS发病无关.     

Immunogenetic factors determining the evolution of T-cell large granular lymphocyte leukaemia and associated cytopenias

T-cell large granular lymphocyte leukaemia (T-LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T-LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immunogenetic predisposition factors, previously described for both immune-mediated bone marrow failure and autoimmune conditions, may promote T-LGL evolution and/or development of cytopenias. The association of T-LGL was analysed with a number of immunogenetic factors in 66 patients, including human leucocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR) genotype, KIR/KIR-L mismatch, CTLA-4 (+49 A/G),CD16-158V/F, CD45 polymorphisms, cytokine single nucleotide polymorphisms including: TNF-alpha (-308G/A), TGF-beta1 (codons 10 C/T, 25 G/C), IL-10 (-1082 G/A), IL-6 (-174 C/G), and IFN-gamma(+874 T/A). A statistically significant increase in A/A genotype for TNF-alpha-308, IL-10-1082, andCTLA-4 +49 was observed in T-LGL patients compared with control, suggesting that the G allele serves a protective role in each case. No association was found between specific KIR/HLA profile and disease. KIR/KIR-L analysis revealed significant mismatches between KIR3DL2 and KIR2DS1 and their ligands HLA-A3/11 and HLA-C group 2 (P = 0.03 and 0.01 respectively); the biological relevance of this finding is questionable. The significance of additional genetic polymorphisms and their clinical correlation to evolution of T-LGL requires future analysis.     

IL-10基因单核苷酸多态性与福建地区非贲门胃癌的相关性研究

目的探讨白细胞介素10（interleukin10，IL-10）启动子区3个位点（IL-1082／-819／-592）的单核苷酸多态性、Mpylori感染与福建地区非责门胃癌之间的相关性。方法采用PCR和直接测序分析来检测IL-10基因多态性；采用胃黏膜快速尿素酶实验检测幽门螺旋杆菌。结果①IL-10．1082位点：胃癌组中A／A型（17．4％）、A／G型（26．4％）、G／G型（9．4％）与对照组相比有统计学意义（P〈0．05）。②IL-10-592位点与IL-10-819位点：胃癌组中C／C基因型（44．8％），C／A基因型（31．2％），A／A基因型（24％）与对照组相比无统计学意义（P〉0．05）。③胃癌患者IL-10-1082、IL-10-592和IL-10-819等位基因分布在H．pylori感染阳性组与阴性组之间，差异无统计学意义（P〉0．05）。结论①IL-10-1082A等位基因与福建地区胃癌发生相关。②IL—10—819／592等位基因与胃癌发生无相关。③IL-10．1082位点、IL-10-819／-592位点等位基因与执pylori感染之间无相关。