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.     

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.     

Association of cytokine gene polymorphisms with bronchial asthma in Macedonians

Bronchial asthma is a multifactorial disease whereby both environmental and genetic factors contribute to its aetiology and/or clinical severity. The aim of this study was to examine the association of 22 cytokine gene polymorphism in the Macedonian population with bronchial asthma (BA). The sample of the population comprised of 301 normal unrelated individuals and 74 patients with BA. Cytokine genotyping was performed by PCR. Susceptible cytokine polymorphisms for BA for ten genotypes (IL-4 -1098/T:T, TNF-alpha -238/A:G, IL-4 -590/C:C, IL-2 +166/T:T, IL-2 -330/T:T, IL-10 -1082/G:G, IFNgamma utr5644/T:T, IL-10 -1082/A:A, IL-1beta +3962/T:T, IL-6 -174/G:G), six diplotypes, four haplotypes, and two alleles were found. Protective cytokine polymorphisms for BA for seven cytokine genotypes (IL-4 -1098/G:T, TNF- alpha -238/G:G, IL-2 -330/G:T, IL-4 -590/C:T, IFNgamma utr5644/A:T, IL-1beta +3962/C:T, IL-10 -1082/A:G), six cytokine diplotypes, four cytokine haplotypes, and four cytokine alleles were found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with BA in population of Macedonians.     

Gene polymorphisms of 22 cytokines in macedonian children with atopic dermatitis

Atopic dermatitis (AD) is a common chronically relapsing skin disease associated with abnormal cytokine production, and activation of T-helper 2 cells. The aim if this study was to determine whether cytokine gene polymorphisms might influence the development of AD. Single nucleotide polymorphisms in the genes for I-L1alpha, IL-1beta, IL-1R, IL-2, IL-4, IL-6, IL-10, IL-12, TGF beta, TNF and IFNgamma were investigated by PCR and sequence specific primers in Macedonian patients with AD (67 children, age of 6 months to 5 years) and 301 normal unrelated individuals. Susceptible cytokine polymorphisms for AD for eleven genotypes (IL-4 -33/T:T IL-4 -1098/G:G, TGFbeta cdn25C:G, IL-4 -1098/T:T, IL-1alpha -889/C:T, IL-2 +166/T:T, IL-1beta -511/C:T, IL-12 -1188/C:T, IL-10 -1082/A:G, IL-1beta +3962/C:T, IFNgamma +874/A:T), five diplotypes, six haplotypes, and for alleles were found. Protective cytokine polymorphisms for AD for seven cytokine genotypes (IL-4 -1098/G:T, TGFbeta cdn25/G:G, IL-4 -33/C:C, IL-1alpha -889/C:C, IFNgamma +874/A:A, IL-10 -1082/A:A, IL-1beta -511/C:C), one cytokine diplotypes, two cytokine haplotypes, and four cytokine alleles were also found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with AD in population of Macedonians.     

The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease

BACKGROUND AND AIMS: Emerging data indicate that alterations in cytokine synthesis may play a role in inflammatory bowel disease (IBD) pathogenesis. The differential production of cytokines has been linked to single nucleotide polymorphisms in gene promoter regions, signal sequences, and gene introns. The aim of this study was to assess the relationship between polymorphisms involving five cytokine genes (TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma), and IBD susceptibility and disease phenotype. METHODS: Cytokine genotyping was performed utilizing polymerase chain reaction. The specific gene polymorphisms that were probed for included: -1082(G/A), -819(T/C), and -592(A/C) in the IL-10 promoter, -308(G/A) in the TNF-alpha promoter, codon 10 (T/C), and codon 25 (G/C) of the TGF-beta signal sequence, +874(T/A) of intron 1 of IFN-gamma, and -174(C/G) in the IL-6 promoter. RESULTS: A total of 193 IBD patients (138 Crohn's disease (CD) and 55 ulcerative colitis (UC)) and 92 controls were evaluated. No association between IBD, UC, or CD susceptibility and the cytokine gene polymorphisms were found. Patients with ileocolonic CD were more likely to possess the IL-6 -174 GG genotype compared to those with nonileocolonic disease (p= 0.006). Patients with ileal CD were more likely to possess the IL-6 -174 GC genotype compared to those with nonileal disease (p= 0.0004). An increased number of CD patients with isolated colonic disease possessed the IL-6 -174 CC genotype compared to those with nonisolated colonic disease (p= 0.032). CONCLUSION: The cytokine gene polymorphisms studied here do not appear to influence IBD susceptibility. There does, however, appear to be an influence on disease phenotype, particularly on CD site.     

IL-6, IL-10 and IL-17 Gene Polymorphisms in Iranian Women with Recurrent Miscarriage

Background: Pro-inflammatory and anti-inflammatory cytokines and polymorphisms of their genes have been described to be involved in the pathogenesis of recurrent miscarriage (RM). Objective: To investigate the association between RM and five polymorphisms of cytokine genes, interleukin 10 (IL-10), (-592 A/C, -819 C/T, -1082 A/G), IL-6 (-174 C/G) and IL-17 (-197 G/A) in Iranian women. Method: Polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) was performed to determine the frequencies of the IL-6, IL-10 and IL-17 gene polymorphisms in 85 women with RM compared with 104 healthy controls. Results: The frequencies of IL- 10 promoter gene polymorphisms (-592 A/C and -819 C/T) were significantly higher in RM women than those in controls (p=0.003). However, no statistically significant differences were observed in the frequencies of IL-6 (-174 C/G), IL-10 (-1082 A/G) and IL-17 (-197 G/A) polymorphisms between RM women and controls. Conclusion: These results suggest that IL-10 gene polymorphism screening might have some relevance in patients with RM, a suggestion which requires further studies.     

白细胞介素10基因启动子-1082A/G及-819T/C多态性与早发冠心病的相关性

目的探讨白细胞介素10(IL-10)基因启动子-1082A/G、-819T/C多态性与中国早发冠心病的相关性。方法早发冠心病(病例组)92例,对照组94例,采用苯酚-氯仿法提取DNA,聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)分析IL-10基因启动子-1082A/G、-819T/C多态性。结果病例组与对照组IL-10-1082A/G,AA、AG、GG基因型频率及A、G等位基因频率差异均无统计学意义(均P>0·05);IL-10-819T/C,TT、TC、CC基因型频率及T、C等位基因频率差异亦均无统计学意义(均P>0·05)。结论IL-10基因启动子-1082A/G和-819T/C多态性可能与中国早发冠心病的易感性无关。     

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.     

Cytokine genotypes correlate with pain and radiologically defined joint damage in patients with juvenile rheumatoid arthritis

OBJECTIVES: Single nucleotide polymorphisms (SNPs) in cytokine genes have been associated with risk of a number of autoimmune diseases. Moreover, some SNPs are associated with variations in rates of in vitro gene expression, and it is therefore possible that these functional polymorphisms may differentially affect inflammatory processes and disease outcome. This project's objective was to determine whether cytokine genotypes correlate with disease outcomes in patients with juvenile rheumatoid arthritis (JRA). METHODS: Genotypes of SNPs of pro-inflammatory cytokines, tumour necrosis factor-alpha -308G -->A, interleukin-6 (IL-6) -174G -->C and interferon-gamma +874G -->A, and anti-inflammatory, immunosuppressive cytokines, interleukin-10 -1082G -->A, -819C -->T and -592A -->C and transforming growth factor-beta1 (TGF-beta1) codon 10T -->C and codon 25G -->C, were determined for patients with JRA who previously participated in a long-term outcome study. Cytokine genotypes and clinical variables showing significant correlations with clinical outcomes at the alpha = 0.100 level in univariate analyses were entered in multivariate tests. RESULTS: In multivariate tests, the IL-6 genotype -174G/G was positively correlated with pain [regression coefficient B = 0.899, 95% confidence intervals (CI) 0.185, 1.612, P = 0.014]. The homozygous TGF-beta1 codon 25G/G genotype showed a protective effect against joint space narrowing on radiographs taken within 2 yr of disease onset, but confidence intervals were wide [odds ratio (OR) 0.176, 95% CI 0.037, 0.837 P = 0.029]. CONCLUSIONS: The correlation of IL-6 genotype with pain and the possible association of the TGF-beta1 codon 25 genotype with short-term radiographic damage (G/C with greater risk and G/G with decreased risk) suggests that both these polymorphisms may be useful early prognostic indicators. Further studies of the relation between cytokine genotypes and outcomes in patients with all forms of juvenile idiopathic arthritis (JIA) are warranted.     

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。     

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。     

Gene polymorphisms of tumor necrosis factor alpha-308 and interleukin-10-1082 among asthmatic Egyptian children.

Tumor necrosis factor (TNF) alpha-308 and interleukin (IL)-10(-1082) have potent inflammatory responses in the process of airway inflammation in asthma. The purpose of this study was to check for association of polymorphisms related to cytokine genes with susceptibility and severity of bronchial asthma in Egyptian children. Blood samples of 69 asthmatic children receiving treatment and follow-up at the Allergy and Respiratory Medicine Unit, Mansoura University Children Hospital, Mansoura, Egypt, were subjected to DNA extraction and amplification using polymerase chain reaction with sequence-specific primers for detection of single nucleotide polymorphisms in the promoter regions of cytokine genes TNF-alpha(-308(G-->A)), IL-10(-1082(G-->A)). Compared with normal controls, Egyptian asthmatic children showed a significant higher frequency of IL-10(-1082) G/G homozygosity genotype (p < 0.001; odds ratio [OR] = 7) with lower frequency of G/A heterozygosity genotype among cases. This finding also was detected in cases with persistent asthma and eczema. These cases showed significant lower frequency of TNF-alpha-308 G/A heterozygosity (p < 0.05; OR = 0.44). Also, male cases, cases with positive family history, and those patients with persistent types of asthma showed a higher frequency of TNF-alpha-308 G/G homozygosity. IL-10(-1082(G-->A)) G/G and TNF-alpha-308(G-->A) G/G may be a contributing factor in susceptibility as well as severity of asthma among Egyptian children. Separate studies should be specified relating these cytokine genotypes to response to various modalities in asthma therapy. This study reports that IL-10(-1082(G-->A)) G/G and TNF-alpha-308(G-->A) G/G genotypes may be contributing factors in susceptibility as well as in severity of asthma among Egyptian children. Separate studies may be specified relating these cytokine genotypes to response to various modalities in asthma therapy.     

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.     

Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection

Host genetic factors have been reported to influence the natural history of hepatitis C virus (HCV) infection. We examined whether variation in interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha) genes would predict the likelihood of sustained response to antiviral therapy. Single nucleotide polymorphisms (SNPs) and microsatellites at two loci encoding the cytokines IL-10 and TNF-alpha were determined by polymerase chain reaction (PCR)-based techniques. Their relationship to the outcome of antiviral therapy for chronic HCV infection was studied in 49 white patients who had a virologically sustained response (SR) and in 55 white nonresponders (NR) to a combination of interferon alfa-2b and ribavirin (IFN + R). Several IL-10 variants were more frequent among SRs compared with NRs. Carriage of the -592A or the -819T SNP was associated with SR (odds ratio [OR] = 2.2; P =.016). The -592A/A and the exclusively linked -819T/T genotypes were also associated with SR (OR = 16.6; P =.013 for either). The haplotype consisting of the 108-bp IL-10.R microsatellite and -3575T, -2763C, -1082A, -819T, -592A was also associated with SR (OR = 2.65; P =.01). Stratification for viral genotype, baseline viral RNA concentration, and histologic status identified homozygosity for the haplotype as the principal determinant: all 5 homozygous individuals achieved SR (OR(crude) = 13.7; P =.025; stratified ORs = 1.9-7.0), whereas heterozygotes differed only slightly from wild-type carriers. In contrast, TNF alleles defined by promoter sequences -238G/A and -308G/A were approximately equally distributed among SR and NR. In conclusion, homozygosity for -592A, -819T or the extended haplotype (108bp) - (-2575T) - (-2763C) - (-1082A) - (-819T) - (-592A) is associated with SR to IFN + R.     

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.     

Influence of interleukin 10 promoter polymorphisms in susceptibility to giant cell arteritis in Northwestern Spain

OBJECTIVE: Proinflammatory cytokines such as interferon-g (IFN-g) play an important role in the pathogenesis of giant cell arteritis (GCA). Interleukin 10 (IL-10) is a Th2 cytokine with a suppressor effect on IFN-g production. We assessed the influence of functional IL-10 gene promoter polymorphisms in susceptibility to GCA in individuals from Northwestern Spain. METHODS: One hundred three patients with biopsy-proven GCA and 226 matched controls from the Lugo region of Northwest Spain were genotyped for IL-10 -1082 G/A (rs1800896) and -592 C/A (rs1800872) promoter single nucleotide polymorphisms (SNP) by Taqman 5' allelic discrimination assay using Taqman predesigned SNP genotyping assays (numbers C_1747360_10 and C_1747363_10, respectively). RESULTS: A significant difference in the distribution of -1082 G/A genotypes between GCA patients and controls was observed (p = 0.034). It was mainly due to a decreased number of GCA patients carrying the -1082 A/A genotype (23.3%) compared with controls (36.7%) [p = 0.01, corrected p (pc) = 0.03; OR 0.53, 95% CI 0.31- 0.90]. In addition, haplotype analysis showed that the ATA haplotype frequency was slightly decreased (p = 0.05, pc = 0.2; OR 0.6, 95% CI 0.4-1.0), whereas the uncommon GTA haplotype was significantly increased in GCA patients compared with controls (p = 0.00005, pc = 0.0002; OR 8.7, 95% CI 2.2-34.8). CONCLUSION Our results suggest a potential implication of IL-10 -1082 promoter polymorphism in susceptibility to GCA in Northwestern Spain.     

Impact of the IL-10 Promoter Gene Polymorphisms in the Severity of Chronic Hepatitis B Infection

Background:

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine. The polymorphisms of its promoter gene have been considered to be related with the chronicity of hepatitis B infection.

Objectives:

The aim of this study was to evaluate the polymorphisms at different positions in the IL-10 promoter gene in patients with chronic hepatitis B.

Patients and Methods:

Totally, 166 patients with chronic hepatitis B infection were enrolled. Genotypes at different positions (i.e. -819, - 592, and - 1082) in the IL-10 gene promoter were determined.

Results:

The C/A genotype at position -592, C/T genotype at position -819, and GCC/ATA haplotype of the IL-10 gene promoter were significantly more common in the patients with cirrhosis. The genotypes were significantly different between the hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients at position -592 (C/A and C/C), position -819 (C/C and C/T), and position -1082 (A/A and G/A).

Conclusions:

Some IL-10 promoter gene polymorphisms predisposed the infected hepatitis B virus cases to cirrhosis in our study population.     

Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin

BACKGROUND/AIMS: In hepatitis C infection, the production of inappropriate cytokine levels appears to contribute to viral persistence and to affect the response to antiviral therapy. Additionally, polymorphisms in the cytokine genes may affect the production of the cytokines. In this study, we determined the frequency of the genotypes associated with polymorphisms of the interleukin-10 and tumor necrosis factor-alpha gene promoters, and transforming growth factor-beta 1 gene leader sequence, and investigated their association with clinical features and the response to interferon-alpha and ribavirin therapy in chronic hepatitis C infection. METHODS: Genomic DNA from 80 patients and 37 racially matched healthy controls was studied by polymerase chain reaction and direct automated sequencing. RESULTS: The interleukin-10 -1082 G/G genotype was identified more frequently in patients than in controls (P=0.048). The transforming-growth factor-beta 1 +29 (codon 10) C/C genotype was associated with resistance to the therapy (P=0.029). After adjusting for potential confounding variables, patients exhibiting the C/C genotype were less likely to respond to treatment than patients with the T/T or T/C genotypes. CONCLUSIONS: These results suggest that inheritance of the interleukin-10 -1082 G/G and the transforming growth factor-beta 1 +29 C/C genotypes, which appear to affect the cytokine production, may be associated with susceptibility to chronic hepatitis C infection and resistance to combined antiviral therapy.