Interleukin-10 -1082A/G polymorphism is associated with the development of acute pancreatitis in a Chinese population

We conducted a case-control study to investigate the association between IL-10 gene polymorphism (-1082A/G, -819T/C, and -592A/C) and risk of acute pancreatitis in a Chinese population. A total of 240 patients with proven acute pancreatitis and 240 control subjects were collected between May 2012 and January 2015. Genotyping of the IL-10-1082A/G, -819T/C, and -592A/C gene polymorphisms was conducted by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. By univariate logistic regression analysis, patients with acute pancreatitis were more likely to have higher BMI (OR=2.12, 95% CI=1.45-3.12; P<0.001) and have a habit of alcohol drinking (OR=2.01, 95% CI=1.37-2.95; P<0.001). There were significant differences in the genotype distributions of IL-10-1082A/G between patients with acute pancreatitis and control subjects (χ²=9.97, P=0.007). By multiple logistic regression analysis, we found that individuals with the GG genotype of IL-10-1082A/G were associated with an increased risk of acute pancreatitis when compared with the AA genotype (OR=2.32, 95% CI=1.20-4.59; P=0.007). In dominant and recessive models, the IL-10-1082A/G gene polymorphism was significantly correlated with an elevated risk of acute pancreatitis, and the adjusted Ors (95% CI) were 1.50 (1.03-2.20) and 1.99 (1.06-3.79), respectively. However, no significant different was found between IL-10-819T/C and -592A/C gene polymorphisms and susceptibility to acute pancreatitis. In conclusion, we suggest that IL-10-1082A/G gene polymorphisms contribute to the development of acute pancreatitis in codominant, dominant and recessive models.     

Association of -592C/A, -819C/T and -1082A/G interleukin-10 promoter polymorphisms with idiopathic recurrent spontaneous abortion

Increasing evidence supports a role for altered T helper 1 (Th1)-Th2 cytokine balance in idiopathic recurrent spontaneous abortion (RSA). The aim of this study was to investigate the association of the interleukin 10 (IL-10) promoter polymorphisms -592C/A, -819C/T and -1082A/G with RSA. Women (n = 350) with at least three consecutive spontaneous abortions (RSA cases) and 200 control women with at least two successful pregnancies were included. The frequency of the -819T allele [P = 0.05, odds ratio (OR) = 1.51], but not other single-nucleotide polymorphisms (SNPs), was higher among RSA patients. Complete linkage disequilibrium (LD) was seen between -592C and -819C and -1082G alleles, as well as between -592A and -819T and between -819C and -1082G alleles only among patients. Although the genotype frequencies (except for -819C/C) of the three polymorphisms were comparable between patients and controls, higher frequency of -592A/-819T/-1082A haplotype (OR = 4.01, 95% CI = 1.83-7.95) was seen in cases versus controls. Regression analysis indicated that, after adjusting for potential variables, -592C/A (OR = 3.32, 95% CI = 1.76-6.27) and -819C/T (OR = 5.06, 95% CI = 2.59-9.91) were associated with exclusively early but not exclusively late RSA, where negative association for both was noted. This supports the notion of involvement of IL-10-592C/A and -819C/T polymorphisms as inherited risk factors of idiopathic RSA.     

Association between IL-10 gene polymorphisms and the risk of ischemic stroke in a Chinese population

We investigated the possible association between two SNPs of IL-10 (IL-10 -1082A/G and -819T/C) and the susceptibility to ischemic stroke. Patients with proven ischemic stroke and control subjects were recruited between March 2013 and May 2015. The IL-10 -1082A/G and -819T/C polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Conditional logistic regression analyses revealed that the GA and the AA genotypes were associated with development of ischemic stroke, and the ORs (95% CI) for the GA and the AA genotypes of IL-10 -1082A/G were 1.49 (1.01-2.19) and 1.83 (1.02-3.29) compared with the GG genotype, respectively. In dominant model, the GA+AA genotype of IL-10 -1082G/A was correlated with increased risk of ischemic stroke compared to the GG genotype (OR=1.56, 95% CI=1.08-2.25). The GA+AA genotype was associated with moderately increased risk of ischemic stroke in smokers (OR=1.72, 95% CI=1.04-2.84). In conclusion, our study suggests that IL-10 gene polymorphisms contribute to the development of ischemic stroke, especially in tobacco smokers.     

Association between Interleukin-10 gene polymorphisms and risk of early-onset preeclampsia

We conducted a case-control study to investigate the role of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) polymorphisms in the development of early-onset preeclampsia. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the polymorphisms of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872). The genotype distributions of IL-10 -1082A/G (rs1800896), -819T/C (rs1800871), and -592A/C (rs1800872) confirmed with HWE in the controls, and the P value for HWE was 0.41, 0.38 and 0.26, respectively. The results of the multivariate logistic regression analysis revealed that the association of individuals expressing the CC genotype and AC+CC of IL-10 -592A/C (rs1800872) with a significantly increased risk of early-onset preeclampsia in co-dominant and dominant models, compared to the AA genotype; the OR (95% CI) for these individuals was determined to be 2.09 (1.12-3.90) and 1.66 (1.03-2.71), respectively. In the recessive model, we found that CC genotype of IL-10 -592A/C (rs1800872) was associated with the increased risk of early-onset preeclampsia when compared with AA+AC genotype (OR = 1.67; 95% CI = 1.01-2.92). In conclusion, our study has indicated that IL-10 -592A/C (rs1800872) polymorphism was associated with an increased risk of early-onset preeclampsia in a Chinese population.     

IL-10 Polymorphisms and Tuberculosis Susceptibility: An Updated Meta-Analysis

Purpose

The association of interleukin-10 (IL-10) polymorphisms (-1082G/A, -819C/T, -592A/C) and interleukin-6 (IL-6) poly-morphisms (-174G/C) with tuberculosis (TB) risk has been widely reported. However, the results are controversial. To clarify the role of these polymorphisms in TB, we performed a meta-analysis of all available and relevant published studies.

Materials and Methods

Based on comprehensive searches of the PubMed, Medline, Embase, Web of Science, Elsevier Science Direct and Cochrane Library database, we identified outcome data from all articles estimating the association between IL-10 and IL-6 polymorphisms and TB risk.

Results

The results indicated significant association of the allele model, heterozygous model and dominant model of IL-6 -174G/C polymorphism with decreased risk of TB. In the stratified analysis by ethnicity, significantly increased risk was observed for IL-10 -1082G/A polymorphism in Europeans under recessive model, for IL-10 -819C/T polymorphism in Asians under heterozygous model and dominant model and IL-10 -592A/C polymorphism in Asians under Allele model, homozygous model and recessive model. Moreover, significantly decreased risk of TB was associated with Asians for IL-6 -174C/G polymorphism in allele model, heterozygous model and dominant model. We also performed the analyses by sample types in IL-10 -1082G/A polymorphism, and observed significantly increased TB risk in mixed group under homozygous model.

Conclusion

The results suggested that the IL-10 -1082G/A polymorphism is associated with increased TB risk in Europeans, while IL-10 -819C/T and IL-10 -592A/C polymorphisms in Asians. However, IL-6 -174G/C polymorphism might be a genetic risk factor that decreases TB susceptibility in Asians.     

Role of IL-10 gene polymorphisms on the susceptibility for esophageal cancer and its association with environmental factors

We conducted a hospital-based case-control study to investigate the association of three common SNPs (-1082G/A rs1800896, -819T/C rs1800871, and -592A/C rs1800872) of IL-10 gene polymorphisms with the susceptibility to esophageal cancer in a Chinese population. 246 patients with pathologically proven esophageal cancer and 492 healthy control subjects were collected in our study. Genotyping of IL-10-1082G/A rs1800896, -819T/C rs1800871, and -592A/C rs1800872 was performed using the Sequenom MassARRAY platform (Sequenom; San Diego, CA). Unconditional logistic regression analyses showed that subjects carrying the AA genotype and GA+AA genotype of IL-10-1082G/A rs1800896 were associated with an increased risk of esophageal cancer, and the adjusted ORs (95% CI) were 2.19 (1.31-3.64) and 1.44 (1.05-1.99), respectively. However, we did not find significant association of IL-10-819T/C rs1800871 and -592A/C rs1800872 with the development of esophageal cancer. By stratification analysis, we found that IL-10-1082G/A rs1800896 polymorphism has no significant association with smoking, drinking and family history of cancer in the first relatives in esophageal cancer risk (P>0.05). In conclusion, IL-10-1082G/A rs1800896 genetic variation may be employed as candidate biomarkers for the prediction of susceptibility in esophageal cancer.     

Relationship between IL-10 gene polymorphisms and the risk of non-Hodgkin lymphoma: A meta-analysis

ObjectivesThe purpose of this study was to explore whether interleukin-10 (IL-10) gene promoter polymorphisms and their haplotypes contribute to the incidence of non-Hodgkin lymphoma (NHL).MethodsA meta-analysis was conducted on the associations of the IL-10-3575T/A, -1082 G/A, -819 C/T, -592C/A polymorphisms and the haplotypes with NHL.ResultsA total of 23 studies involving 21,563 NHL patients and 23,837 controls were included in the meta-analysis. Pooled results indicated that IL-10-3575T/A was associated with an increased risk of NHL based on the dominant model (OR: 1.095, 95% CI: 1.020–1.178), similar results were found for -1082A/G in the heterozygous and recessive models (OR: 1.042, 95% CI: 1.012–1.074; and OR: 1.034, 95% CI: 1.011–1.057, respectively). In the ethnic subgroup analysis, -3575T/A had an increased risk of NHL in Caucasians based on the homozygous model (OR: 1.071, 95% CI: 1.001–1.146), and similar results were found for -1082A/G in the heterozygous and recessive models (OR: 1.041, 95% CI: 1.009–1.075; and OR: 1.031, 95% CI: 1.008–1.055, respectively). When stratified by subtypes, -3575T/A and -1082A/G polymorphisms were found significant association with an increased risk of B cell lymphoma, specifically diffuse large B-cell lymphoma (DLBCL). Moreover, -3575T/A was associated with an increased risk of follicular lymphoma (FL) in the homozygous and recessive models. Furthermore, we observed that significantly increased risk of NHL and DLBCL were associated with the A-G-C-C haplotype (IL-10-3575T/A, -1082A/G, -819C/T and -592C/A), and a decreased risk of DLBCL subtype was associated with the T-A-C-C haplotype.ConclusionsIL-10-3575T/A and -1082A/G polymorphisms were associated with altered NHL susceptibility, especially for Caucasians and B cell lymphoma. IL-10 (-3575T/A, -1082A/G, -819C/T and -592C/A) haplotype were associated with NHL and DLBCL subtype.     

Association between interleukin-10 -1082A/G, -819C/T and -592C/A polymorphisms with deep venous thrombosis

Background

Deep venous thrombosis (DVT) and inflammation are two closely related entities. The objective of this study was to evaluate a possible association between interleukin-10 (IL-10) -1082A/G, -819C/T and -592C/A polymorphisms with DVT.

Methods

A case-control study was carried out in 660 patients with DVT and 660 age- and gender-matched healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) assay was applied to identify the polymorphisms mentioned.

Results

Patients with DVT had a significantly lower frequency of IL-10 -1082GG genotype [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.39, 0.89; P = 0.01] than healthy controls. When stratifying by family history of DVT, it was found that patients with positive family history of DVT had a significantly lower frequency of IL-10 -1082GG genotype (OR = 0.13, 95% CI = 0.02, 0.95; P = 0.04). When stratifying by smoking status, presence of varicose veins, type 2 diabetes mellitus and any hormone administration before, no significant differences were found in any groups.

Conclusions

This study provides evidence that IL-10 -1082A/G polymorphism associated with risk of DVT. However, no association of the IL-10 -592C/A or -819C/T polymorphism with DVT risk was found. Additional well-designed large studies were required for the validation of our results.     

Effect of interleukin-10 gene promoter polymorphisms -1082 G/A and -592 C/A on response to therapy in children and adolescents with chronic hepatitis C virus infection

Background and aimStudying predictors of response to therapy for hepatitis C virus (HCV) infection in children may help avoid the inappropriate use of currently available costly therapy associated with numerous adverse effects. We tested the hypothesis that inheritance of single nucleotide polymorphisms (SNPs) of the interleukin-10 (IL-10) promoter gene might influence response to HCV treatment.Patients and methodsThe impact of SNPs, -1082 G/A and -592 C/A, in the promoter region of IL-10 gene, on response to HCV therapy was assessed in a cohort of 40 children treated with a combination of pegylated interferon (Peg-IFN) α2b and ribavirin.ResultsSustained virological response was achieved in 48.7%. High viral load was associated with non-response to therapy. There was no association between histopathological degree of inflammation or fibrosis and response to therapy. There was no direct statistically significant association between polymorphisms in the IL-10 gene (-1082G/A and -592 C/A) as regards inflammation or response to therapy in children. As for the SNP -592 C/A; there was a statistically significant association with the score of fibrosis (P < 0.004), concluding that the A allele was protective from moderate and severe fibrosis. Meanwhile the SNP -1082G/A did not show any association with the fibrosis score.ConclusionWe could not associate response to therapy for HCV with IL-10 polymorphisms -1082 G/A and -592 C/A. For the SNP -592 C/A, the A allele protected from moderate and severe fibrosis.     

Association between the Interleukin-10 -1082 G/A polymorphism and risk of hepatocellular carcinoma

BackgroundInconsistent results have been reported from studies investigating the relationship of the interleukin-10 (IL-10) -1082 G/A polymorphism and the susceptibility of hepatocellular carcinoma (HCC). Therefore, a thorough literature review of relatedstudies was performed in this meta-analysis to examine the association of the interleukin-10(IL-10) -1082 G/A polymorphism with HCC susceptibility.MethodsElectronic databases were searched for literature on the relationship between interleukin-10(IL-10) -1082 G/A polymorphism and the risk of HCC in accordance with the inclusion and exclusion criteria. The selected studies were analyzed using the Stata 12.0 software. Finally, the strength of the associations was evaluated using the odds ratio (OR) and 95% confidence intervals (95% CI).ResultsA total of six case-control studies were enrolled into the current meta-analysis, which included a total of 911 patients and 1889 control subjects. Our data revealed no association between the IL-10 -1082 G/A polymorphism and the risk of HCC (GG vs AA:OR=0.84, 95%CI=0.57–1.25; AG vs AA:OR=0.85, 95%CI=0.70–1.05; Dominant model: OR=0.85, 95%CI=0.70–1.03; and Recessive model: OR=0.92, 95%CI = 0.64–1.32). Similarly, no association was found in sub-group analysis based on ethnicity.ConclusionThe results of our study suggest no association between IL-10 -1082 G/A polymorphism and the risk of HCC.     

Association between interleukin-10 gene promoter polymorphisms and susceptibility to liver cirrhosis

We conducted a case-control study to investigate the association between three common SNPs in IL-10 gene (rs1800896, rs1800871 and rs1800872) and the development of liver cirrhosis in a Chinese population. Between January 2013 and December 2014, a total of 318 patients with liver cirrhosis and 318 health control subjects were enrolled into our study. The IL-10 rs1800896, rs1800871 and rs1800872 polymorphisms were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By multivariate logistic regression analysis, we found that individuals with the AA genotype and GA+AA genotype of IL-10 rs1800896 were more likely to have an increased risk of liver cirrhosis when compared with the GG genotype, and the ORs (95% CI) for the AA genotype and GA+AA genotype were 2.04 (1.20-3.50) and 1.41 (1.02-1.96), respectively. We found that the GA+AA genotype of IL-10 rs1800896 had higher risk of liver cirrhosis in individuals with chronic hepatitis B when compared with the GG genotype (OR = 1.95, 95% CI = 1.01-3.59). In conclusion, we found that IL-10 rs1800896 polymorphism was correlated with an increased risk of liver cirrhosis, especially in individuals with chronic hepatitis B.     

Analysis of IL-10 and IL-6 Gene Polymorphisms and Their Serum Levels in Patients with Brucellosis: A Case Control Study

Background: It seems that polymorphism in the regulatory areas of cytokine genes affects the cytokine production capacity and may play a role in the development of infectious diseases. Interleukin-10 (IL-10) and Interleukin-6 (IL-6), which are cytokines of Th₂, cause the macrophage become inactive and patient conditions get worse.

Methods: In this case‐control study, 60 patients with brucellosis and 60 healthy participants were recruited. IL-10 genotyping at positions -1082 (G/A), -819 (C/T), and -592 (C/A) and IL-6 genotyping at position -174 (G/C) were analyzed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods. The levels of IL-10 and IL-6 were determined by a sandwich enzyme-linked immunosorbent assay in sera of study population.

Results: The AA and CC genotypes of the IL-10 gene at positions -1082 G/A and -819 C/T were significantly more frequent in patients in comparison to controls, respectively. The AG genotype of the IL-10 gene at positions -1082 G/A was significantly more frequent in control groups than the patients. Serum levels of IL-10 and IL-6 were significantly more frequent in the patients than in the control groups.

Conclusions: Our study showed that the AA and CC genotypes at positions -1082 and -819 are very important, respectively. These results suggest that IL-10 (-1082 G/A) GG genotype may be considered as a risk factor for brucellosis, while the AG genotype might be a protective factor against the disease.     

Interleukin-10 gene promoter polymorphism in Polish rheumatoid arthritis patients

Interleukin (IL)-10 is an important multifunctional cytokine with both anti-inflammatory and immunoregulatory effects in rheumatoid arthritis (RA). In the present study, we evaluated the frequency and potential impact of IL-10 promoter polymorphisms on susceptibility to and severity of RA in Polish in – patients with a high disease activity (mean DAS 28 C-reactive protein 5.25). DNA was obtained from 244 RA patients and 106 healthy controls. The −592C/A and −1082G/A IL-10 gene polymorphisms were amplified by polymerase chain reaction with restriction endonuclease mapping. The frequency of the IL-10-592CA, -592AA genotypes (respectively: 30% vs 5% and 7% vs 0%) and allele −592A (37% vs 5%) were significantly higher in RA patients as compared with a control group. We did not find any association of the IL-10-592C/A genotype distribution with disease parameters, except for an increased ESR (erythrocyte sedimentation rate) in patients with the −592CC genotype as compared with those with −592CA or −592AA genotypes (P = 0.01). The frequency of the IL-10-1082GG genotype was lower (P = 0.0001), and that of the IL-10-1082GA genotype was higher (P = 0.009) in RA patients comparing with the control group. In RA patients with −1082GA or −1082AA genotypes the time duration of the disease (P = 0.03), Health Assessment Questionnaire (HAQ) Score (P = 0.04) and PLT count (P = 0.001) were significantly increased as compared with subjects with −1082GG genotype. Presented findings indicate that IL-10-592C/A and IL-10-1082G/A polymorphisms may be considered genetic risk factors for RA susceptibility and severity.     

Single Nucleotide Polymorphisms in IL-10, IL-12p40, and IL-13 Genes and Susceptibility to Glioma

Glioma is one of the most aggressive and most common tumors of the central nervous system (CNS) in humans. The exact causes of glioma are not well known, but evidence suggests the involvement of genetic factors in addition to environmental risk factors. The present study aimed to determine whether polymorphisms in IL-10-1082A/G, IL-12p40 1188C/A, and IL-13+2044G/A (rs20541) are associated with the incidence of glioma in Iraqi patients. Ninety-six patients with different grades of glioma and 40 apparently healthy individuals were recruited. A blood sample and genomic DNA were collected from all subjects. The amplification refractory mutation system and sequence-specific primer polymerase chain reaction (PCR) were used for genotyping of IL-10-1082A/G and IL-12p40 1188C/A, respectively; whereas, the IL-13+2044G/A was detected by DNA sequencing after amplification of the genes by PCR.All SNPs were within Hardy-Weinberg equilibrium and each appeared in three genotypes in patients and controls. In IL-10-1082A/G, these genotypes frequencies were AA (75%), AG (22.93%) and GG (2.07%) in patients as compared to similar frequencies (62.5%), (27.5%) and (10%) respectively, in controls. The variant IL-12p40 1188C/A genotype was AA (72.92%), AC (23.96%), and CC (3.13%%) in patients as compared to 65%, 30%, and 5%, respectively, in controls. The frequencies of IL-13+2044G/A genotypes (GG, GA, and AA) were 89.58%, 9.37%, and 1.04% among patients versus 47.5%, 32.5% and 20%, respectively, among controls. These results suggest a protective role of mutant alleles G and A in IL-10-1082A/G and IL-13+2044G/A against gliomas. Further studies with more rigorous parameter designs will be needed to confirm the current findings.     

Interleukin-10 gene polymorphisms influence the clinical course of non-Hodgkin's lymphoma

The pathophysiology of Non-Hodgkin's lymphoma (NHL) is still unknown and clinical course is very unpredictable. Many cytokines, including interleukin-10 (IL-10), play a role in the perpetuation of this disease. The IL-10-producing capability has been found to be influenced by the IL-10 gene promoter polymorphisms. The aim of the present study was to assess whether any of IL-10 (-1082 A/G, -819 C/T and -592 A/C) genotypes prevails in Polish patients with NHL and whether IL-10 promoter polymorphisms may be associated with less or more favourable course of the disease. IL-10 gene promoter polymorphisms were assessed in 105 individuals, including 55 NHL patients and 50 ethically matched controls. The frequency of the IL-10 low-producing -1082 AA homozygous genotype was significantly higher in patients with aggressive NHL as compared with patients with indolent forms of the disease (0.57 vs 0.28, P < 0.05) and controls [0.57 vs 0.32, odds ratio (OR) = 2.69, P < 0.05]. Also, the presence of the ACC genotype was more frequently detected among patients with more aggressive disease than in those with indolent forms (0.74 vs 0.47, P < 0.05) and healthy controls (0.74 vs 0.42, OR = 3.69, P < 0.05). In multivariate analyses, the AA homozygosity (OR = 6.33, P < 0.05) and ACC genotype (OR = 3.57, P = 0.05) appeared as independent risk factors of more aggressive manifestation of NHL in addition to the elevated lactate dehydrogenase 480 level. Although no direct association was found between IL-10 promoter polymorphisms and NHL, IL-10 (-1082) AA homozygosity and IL-10 ACC genotype were found to be associated with unfavourable prognosis in patients with NHL.     

The combined effect of interleukin (IL)-10 and IL-12 polymorphisms on induced cytokine production

Interleukin (IL)-12 and IL-10 are immunoregulatory cytokines with an antagonistic effect of the T-helper (Th)1/Th2 cytokine balance and provide a functional link between innate and adaptive immune responses. The aim of the study was to investigate the combined effect of -1082A*G in IL10 and +16974A*C in IL12B single nucleotide polymorphisms (SNPs) on induced cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. The presence of the high-producer IL-12p40 genotype led to diminished production of IL-10 as determined by the -1082*G allele of SNP in IL10. Significantly decreased IL-10 production was detected in AA+AG/GG in comparison with the low-producer IL-12p40 (AC/CC+AG/GG) genotype combination after stimulation with C3bgp (2 +/- 4 vs. 29 +/- 14.2 pg/ml; p = 0.0003) and LPS (33.4 +/- 13.5 vs. 93.3 +/- 59.6 pg/ml; p = 0.019). IL-12p40 production was independent of IL10 genotype. The present results demonstrated that the production of IL-10 from PBMC depended on both -1082A*G in IL10 and +16974A*C in IL12B polymorphisms.     

Interleukin-17A gene polymorphism is associated with susceptibility to gastric cancer

We conducted a study to investigate the role of three common SNPs in the IL-17A and IL-17F genes (rs2275913G>A, rs3748067C>T and rs763780T>C) in the development of gastric cancer, and their interaction with H.pylori infection. A total of 326 patients with gastric cancer and 326 control subjects were consecutively recruited between May 2012 and May 2014. Genotyping of IL-17A rs2275913G>A and rs3748067C>T and IL-17F rs763780T>C was performed in a 384-well plate format on the Sequenom MassARRAY platform. By logistic regression analysis, individuals carrying the GA and AA genotypes of IL-17 rs2275913G>A were significantly associated with an increased risk of gastric cancer when compared with GG genotype, and the adjusted Ors (95% CI) were 1.46 (1.03-2.06) for GA genotype and 2.57 (1.51-4.43) for AA genotype. We observed that the GA+AA genotype of rs2275913 was associated with an increased risk of gastric cancer among H.pylori infection subjects (OR=2.21, 95% CI=1.29-3.79). In conclusion, we found that there was a significant association between L-17A rs2275913G>A polymorphism and increased gastric cancer risk, especially in H.pylori infection subjects.     

The interleukin-10-1082 promoter polymorphism and cancer risk: a meta-analysis

Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and anti-angiogenic properties and play an important role in the pathogenesis of cancer. IL-10-1082A>G polymorphism is the most extensively studied polymorphism in the IL-10 gene in cancer susceptibility. To date, a number of case-control studies were conducted to investigate the association between IL-10-1082A>G polymorphism and cancer risk in humans. However, the association between the IL-10-1082A>G polymorphism and cancer risk is still ambiguous. In an effort to solve this controversy, we performed a meta-analysis based on 61 case-control studies, including 14,499 cancer cases and 16,967 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. In the stratified analyses by specific cancer type, increased risk was found in lung cancer (OR = 3.16, 95% CI = 1.16-8.63 for GA versus AA; OR = 2.07, 95% CI = 1.16-3.70 for GG versus AA; OR = 3.17, 95% CI = 1.31-7.68 for GA/GG versus AA) and non-Hodgkin's lymphoma (OR = 1.18, 95% CI = 1.02-1.36 for GA versus AA; OR = 1.17, 95% CI = 1.02-1.35 for GA/GG versus AA). The meta-analysis also indicated that the variant genotypes were associated with a moderately increased risk in Asians in all genetic models (OR = 1.80, 95% CI = 1.17-2.76 for GA versus AA; OR = 3.32, 95% CI = 1.62-6.82 for GG versus AA; OR = 1.67, 95% CI = 1.07-2.60 for GA/GG versus AA; OR= 2.93, 95% CI = 1.43-6.03 for GG versus AA/GA). The meta-analysis suggested that the IL-10-1082A>G polymorphism was associated with increased risk of cancer in Asians and lung cancer and non-Hodgkin's lymphoma. To draw comprehensive and true conclusions, more researches with larger numbers of worldwide participants are needed to examine associations between IL-10-1082A>G polymorphism and cancer risk.     

Association between CTLA-4 gene polymorphism and ankylosing spondylitis: a case-control study

Aims: The aim of our study was to evaluate the association between CTLA-4 polymorphisms (+49A/G, -318C/T and CT60A/G) and ankylosing spondylitis (AS) susceptibility. Methods: A total of 120 AS cases and healthy controls, matched on the age and gender, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) were used to determine the gentypes of +49A/G, -318C/T and CT60A/G polymorphisms. Genotype distribution in control group was assessed by Hardy Weinberg Equilibrium (HWE) test. Odds ratio (OR) with 95% confidence interval (95% CI) were adopted to evaluate the relationship of CTLA-4 polymorphisms and AS susceptibility. Results: In our study, genotype distribution of the three polymorphisms in control group was consistent with the HWE (P > 0.05). The genotype analysis showed that AA genotype of + 49A/G polymorphism could increase the risk for AS (OR=2.357, 95% CI=1.127-4.930). Moreover, the frequency of A allele was also presented as a risk factor for AS. Additionally, AA genotype and A allele of CT60A/G appeared to be related with AS susceptibility (OR=2.610, 95% CI=1.047-6.510; OR=1.751, 95% CI=1.160-2.641). However, the T allele of -318C/T appeared to be a protective factor for AS (OR=0.383, 95% CI=0.228-0.643). Conclusion: In summary, there existed significant association between CTLA-4 gene polymorphisms and increased or decreased risk for AS.     

Interleukin-10 gene promoter polymorphisms and the risk of nasopharyngeal carcinoma

Genetic factors are known to be important in the development of nasopharyngeal carcinoma (NPC). Interleukin-10 (IL-10) is an immunosuppressive cytokine which may facilitate development of cancer by supporting tumor escape from the immune response. Interindividual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) at positions -1082 (A/G), -819 (T/C) and -592 (A/C) in the IL-10 gene promoter were involved in predisposing an individual to NPC. One hundred and ninety-eight patients with NPC and 210 age- and sex-matched controls, genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. There were significantly differences in the genotype and allele distribution of -1082 A/G polymorphism of the IL-10 gene among cases and controls. The -1082 AG and GG genotypes were associated with a significantly increased risk of NPC as compared with the -1082 AA genotypes. Haplotype analysis showed that the homozygosity of the GCC haplotype (defined by SNPs at positions -1082, -819 and -592) of IL-10 gene conveys the highest risk for NPC compared with the homozygosity for the ATA haplotype. This study shows for the first time an association between IL-10 gene promoter -1082 A/G polymorphism and its haplotype may contribute to genetic susceptibility to NPC in a Chinese population.