Interleukin-10 Gene Polymorphisms in Recurrent Aphthous Stomatitis

Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease with unknown etiology in which the immune system seems to have a role in oral tolerance. Interleukin (IL)-10 is a cytokine synthesis inhibitory factor. Single nucleotide polymorphisms (SNPs) of IL10 gene could alter this cytokine production. The aim of this study was to investigate frequencies of IL10 alleles and genotypes in a group of individuals with RAS. Genomic DNA of 60 Iranian patients with RAS were typed for IL10 gene (C/A ?1082, C/T ?819, and C/A ?592), using PCR-SSP method. Frequency of each allele and genotype was compared to control group.

A significantly higher frequencies of the T allele at position ?819 (p?=?0.006) and the A allele at position of ?592 (p?<?0.001) were found in the patients with RAS group, when compared to the controls. IL10 GA genotype at position ?1082 (p?=?0.007), CA genotype at position ?592 (p?=?0.001), and CT genotype at position ?819 (p?=?0.001) were significantly higher in the RAS patients. The results of this study suggest that certain SNPs of IL10 gene have association with predisposition of individuals to RAS. However, further multicenter studies should be conducted to confirm the results of this study.     

Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease

Among genetic factors that may contribute to the development and progression of Graves’ disease (GD) and its complications are polymorphisms in the genes encoding cytokines. The association between GD and the following polymorphisms in anti-inflammatory cytokines was studied in 107 patients with GD and 140 healthy controls: IL-4 (−1098T/G, −590T/C, −33C/T), IL-10 (−1082A/G, −819C/T, −592C/A) and TGF-β (+869T/C, +915G/C). The following alleles and genotypes were significantly (P < 0.01 after correction for multiple testing) more frequent among patients: the IL-4 −1098G allele and GG genotype (OR = 3.12 and 105.00, respectively), IL-4 −33T allele and TT genotype (OR = 2.52 and 118.83, respectively), IL-10 −1082G allele and GG genotype (OR = 2.16 and 6.40, respectively), IL-10 −819T allele, TC and TT genotype (OR = 2.60, 3.68 and 6.76, respectively), IL-10 −592A allele, AC and AA genotype (OR = 2.41, 2.89 and 5.68, respectively), TGF-β +869C allele and CC genotype (OR = 2.24 and 6.21, respectively), and TGF-β +915C allele, CG and CC genotype (OR = 7.81, 11.80 and 20.40, respectively). The only allele and genotype with a lower frequency in patients were IL-4 −590T allele and TC genotype (OR = 0.47 and 0.08, respectively; P < 0.01). In conclusion, this study highlighted the importance of anti-inflammatory cytokine gene polymorphisms in susceptibility to GD.     

Genetic Association of IL-10 Gene Promoter Polymorphism and HIV-1 Infection in North Indians

Introduction  Cytokines play a significant role in host immune defense. IL-10 is an anti-inflammatory, immunomodulatory cytokine that can both stimulate and suppress the immune response and inhibits HIV-1 replication in vivo. Interindividual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. Aims  The aim of this study was to investigate the association of IL-10 gene promoter −1082 G/A, −819 C/T, and 592 C/A polymorphism on HIV-1 transmission /progression in North Indian individuals. Patients and Methods  A total of 180 HIV-1 seropositive (HSP) stratified on the basis of disease severity (stage I, II, and III), 50 HIV-1 exposed seronegative (HES) and 305 HIV-1 seronegative (HSN) individuals were genotyped for IL-10 gene promoter by polymerase chain reaction-restriction fragment length polymorphism. A suggestive evidence of association was obtained for IL-10 592 C/A promoter polymorphism at the level of allele and genotype distribution. The frequency of IL-10 592 A allele and genotype was significantly increased in HSP compared to HSN (p = 0.013; OR = 1.412 and p = 0.034; OR = 1.685 respectively). Further comparison in between different clinical stages of HIV-1 infected patients of IL-10 592 A allele and genotype revealed a significant increase in its frequency in the stage III compared with those together in stage I (p = 0.004, OR = 2.181 and p = 0.002, OR = 4.156, respectively). This study reports for the first time that IL-10 gene promoter 592 C/A polymorphism may be a risk factor for HIV-1 transmission/progression in HIV-1 infected North Indian individuals.     

Association of CTLA‐4, TNF alpha and IL 10 polymorphisms with susceptibility to hepatocellular carcinoma

Our aim was to evaluate the association of genetic polymorphisms of immunoregulatory molecules with susceptibility to hepatocellular carcinoma (HCC). The polymorphisms in CTLA‐4 (?318 T/C, CT60 G/A), TNF (?238 G/A, ?308 G/A) and IL10 (?592 C/A, ?819 C/T) were genotyped by PCR and DNA sequencing. The functional relevance of the polymorphisms was examined by ELISAs, in vitro lymphocyte proliferation assay and cytotoxic assay. The CTLA‐4 ?318 TC/TT, CTLA‐4 CT60 GG, IL10 ?592 CA and ?819 CT/TT variants, CTLA‐4 ?318 T and IL 10 ?819 T alleles were positively associated with HCC risk (P < .05). While TNF ?238 AA variant, TNF ?238 A allele were associated with decreased risk of HCC (P < .05). Furthermore, combinations of CTLA‐4 ?318 TC/TT and TNF ?238 GG/GA; CTLA‐4 ?318 TC/TT and IL 10 ?819 CC; CTLA‐4 ?318 CC and IL 10 ?819 CT/TT in patients with HCC were statistically significant (P < .05). Peripheral blood mononuclear cells (PBMCs) carrying ?318 TC/TT genotypes exhibited significantly lower proliferation rates, decreased IL‐2, IL‐4 levels, fewer cytolytic activities and elevated TGF‐β levels. For IL 10 ?819 C/T, the CC genotype was significantly associated with higher proliferation rate, decreased TGF‐β, IL‐10 levels and higher cytolytic activities (P < .05). For TNF ?238 G/A, the AA genotype only had association with serum IL‐2, IL‐4 (P < .05). In addition, we also found that CTLA‐4 ?318 T/C, IL‐10 ?819 T/C variants, combinations of CTLA‐4 ?318 CC with IL 10 ?819 CT or TT, CTLA‐4 ?318 TC or TT with IL 10 ?819 CT or TT were associated with the severity of HCC. These findings suggest that CTLA‐4 ?318 TC/TT and IL 10 ?819 CT/TT could promote the pathogenesis of HCC, which might be related with down‐regulation of Th1/Th2‐type cytokines and/or up‐regulation of Th3‐type cytokines.     

Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

The study determined whether interleukin-10 (IL-10) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and SLE.

Results

A total of 19 studies involving 2828 SLE patients and 4008 controls were considered in the meta-analysis. Meta-analysis of the IL-10-1082 G/A polymorphism revealed an association between SLE and the IL-10-1082 G allele (odds ratio [OR] = 1.158, 95% confidence interval [CI] = 1.051–1.276, p = 0.003). Stratification by ethnicity indicated an association between the IL-10-1082 G allele and SLE in Europeans (OR = 1.160, 95% CI = 1.039–1.296, p = 0.008). Meta-analysis stratified by ethnicity produced an association between the IL-10-819 C allele and SLE in Asians (OR = 1.308, 95% CI = 1.030–1.619, p = 0.027). Meta-analysis of the homozygous GCC/GCC haplotype failed to show a significant association with SLE in Europeans (OR = 1.223, 95% CI = 0.981–1.526, p = 0.074). However, meta-analysis of the GCC haplotype revealed a significant association with RA in all study subjects (OR = 1.402, 95% CI = 1.001–1.964, p = 0.049). Stratification by ethnicity indicated an association between the GCC haplotype and SLE in Europeans (OR = 1.656, 95% CI = 1.087–2.523, p = 0.019), but not in Asians (OR = 1.100, 95% CI = 0.703–1.721, p = 0.677). Meta-analysis of homozygous ATA/ATA haplotype failed to show a significant association with SLE in overall and European groups. However, meta-analysis of the ATA haplotype revealed a significant association with SLE in all study subjects (OR = 1.516, 95% CI = 1.039–2.213, p = 0.031) and Asians (OR = 2.580, 95% CI = 2.086–3.192, p < 1 × 10⁻⁹), but not in Europeans (OR = 1.233, 95% CI = 0.816–1.862, p = 0.320).

Conclusions

This meta-analysis suggests that the IL-10 polymorphisms confer susceptibility to SLE in Europeans and in Asians.     

IL‐1A rs1800587, IL‐1B rs1143634 and IL‐1R1 rs2234650 polymorphisms in Iranian patients with systemic sclerosis

Systemic Sclerosis (SSc) is a systemic autoimmune disorder, with ambiguous pathogenesis. Genetic and environmental factors were proved to be correlated with SSc aetiology. Single nucleotide polymorphisms (SNPs) in cytokine genes can alter the structure and function of the cytokines and consequently may increase the susceptibility to a specific disease. In this study, we investigated SNPs of the IL‐1 gene cluster in Iranian SSc patients. We obtained blood samples from 170 SSc patients and 213 healthy individuals. Cytokine genotyping results were obtained by polymerase chain reaction with sequence‐specific primers (PCR‐SSP). IL‐1A rs1800587, IL‐1B rs1143634 and IL‐1R1 rs2234650 were evaluated for SNP study. The frequency of the IL‐1B rs1143634 CT genotype was significantly lower in SSc patients compared to the controls (OR = 0.584; 95% CI = 0.385–0.886; P‐value = 0.023), so we propose that CT genotype of this allele might be protective. According to our haplotype analysis, CCC haplotype frequency is higher in the control group compared to SSc patients (OR = 1.575; 95% CI = 1.176–2.111; P‐value = 0.008) and in contrast, CTC haplotype frequency is lower in the control group compared to SSc patients (OR = 0.152; 95% CI = 0.047–0.484; P‐value = 0.002), so they might decrease and increase the susceptibility of having SSc, respectively. In addition, we reported two significant diplotypes frequency differences among SSc patients and healthy individuals. It is highly important that there is not much resemblance between the IL‐1 gene cluster polymorphism in different populations, so we can indicate that SNPs may play critical roles when they are combined with other genetic and environmental factors.     

Association of Interleukin 10 Gene Polymorphisms with Autoimmune Thyroid Disease: Meta‐Analysis

The aim of this study was to perform a meta‐analysis of eligible studies and to derive a precise estimate of the association between interleukin 10 (IL10) polymorphisms and susceptibility to autoimmune thyroid disease (AITD). Meta‐analyses were conducted on the associations between AITD and the ‐1082 G/A (rs1800896), ‐819 C/T (rs1800871) and ‐592 C/A (rs1800872) polymorphisms in IL10, and the haplotype of these polymorphisms and AITD. A total of 2903 AITD patients and 3060 controls in 10 eligible studies were included in the meta‐analysis. This meta‐analysis showed significant associations between IL10 at the ‐1082 G allele and overall AITD (OR: 1.44, 95% CI 1.13–1.82, P = 0.003), but no association between the IL10 ‐592 C allele and the ‐819 C allele and AITD. Subgroup studies demonstrated significant associations between the ‐1082 G allele and susceptibility to Graves’ disease. Ethnicity‐specific meta‐analysis revealed significant associations between the ‐1082 G allele and AITD susceptibility in Asian populations; however, in Middle Eastern populations, no association was evident. Meta‐analysis of the IL10 haplotype revealed an association between the ATA haplotype and AITD (OR: 1.17, 95% CI 1.00–1.36, P = 0.04). Meta‐analysis demonstrates that the IL10 polymorphisms are associated with susceptibility to AITD.     

Association of IL‐1β +3954 C/T and IL‐10‐1082 G/A Cytokine Gene Polymorphisms with Susceptibility to Tuberculosis

Tuberculosis (TB) constitutes the major cause of death due to infectious diseases. Cytokines play a major role in defence against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Household contacts (HHC) are at increased risk of developing the disease. In this study, we examined the association of IL‐1β and IL‐10 cytokine gene polymorphisms with risk of developing tuberculosis in TB patients, their HHC and healthy controls (HC) using JavaStat and SPSS. Multifactor dimensionality reduction (MDR) analyses were performed to explore the potential gene–gene interactions. The genotype and allele frequencies of IL‐1β +3954C/T polymorphism did not vary significantly between TB patients and HC. GG (P < 0.005, OR = 0.219 and 95% CI = 0.059–0.735) and GA (P < 0.0001, OR = 2.938 and 95% CI = 1.526–5.696) genotypes of IL‐10‐1082 G/A polymorphism were found to be significantly associated with patients versus HC. HHC with CC (P < 0.03, OR = 1.833 and 95% CI = 1.1–3.35) genotype in IL‐1β and GA (P < 0.0001, OR = 4.612 and 95% CI = 2.225–9.702) genotype in IL‐10 were at increased risk of developing tuberculosis. MDR tests revealed high‐risk genotypes in IL‐1β and IL‐10 based on the association model. Our results demonstrate that the polymorphisms of IL‐1β and IL‐10 genes may be valuable markers to predict the risk for the development of TB in household contacts.     

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.     

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.     

ICOS gene polymorphisms in systemic lupus erythematosus: A case–control study

The inducible T-cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen-presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case–control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (−693 G/A) and rs10932029 (IVS1 + 173 T/C); using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss .20. Our results revealed a significant association between ICOS gene rs11889031 > CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p = .001, odds ratio [OR] = 2.18 IC [1.36–3.49]); codominant genetic model 2, (C/C vs. T/T) p = .007, OR = 15.29 IC [1.97–118.5]); dominant genetic model, (C/C vs. C/T + T/T) p = .0001, OR = 2.44 IC [1.53–3.9]). Besides, there was a marginal association between rs11889031 > TT genotype and T allele with a protective role from SLE (recessive genetic model, p = .016, OR = 0.08 IC [0.01–0.63] and p = 7.6904E − 05, OR = 0.43 IC = [0.28–0.66], respectively). Moreover, statistical analysis indicated that the rs11889031 > CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti-SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031 > CC genotype with SLE, in contrast to a protective effect of rs11889031 > TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker.     

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population,a preliminary report

Several lines of evidence support an association between tropomyosin 1 (TPM1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present study aimed to investigate the association between TPM1 polymorphisms and the risk of NSCL/P in an Iranian population. This case‐control was done on 105 NSCL/P patients and 110 unrelated healthy controls. TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 polymorphisms were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism method. The finding showed that rs11071720 polymorphism significantly increased the risk of NSCL/P in homozygous codominant (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.14–5.69, p = 0.023, TT vs. CC), recessive (OR = 2.33, 95% CI = 1.06–5.18, p = 0.021, TT vs. CT + CC), and allele (OR = 1.53, 95% CI = 1.02–2.30, p = 0.030, T vs. C). The rs12148828 polymorphism was associated with protection against NSCL/P in codominant (OR = 0.27, 95% CI = 0.15–0.48, p < 0.001, TC vs. TT) and allele (OR = 0.38, 95% CI = 0.22–0.64, p < 0.001, C vs. T). Regarding rs3803499, the findings proposed that this polymorphism significantly increased the risk of NSCL/P in codominant (OR = 3.86, 95% CI = 1.19–12.56, p = 0.025, CC vs. TT) and recessive (OR = 3.74, 95% CI = 1.09–14.15, p = 0.018, CC vs. CT + TT). No significant association was practical between rs1972041 polymorphism and NSCL/P. In conclusion, the findings proposed that TPM1 polymorphisms may contribute to the etiology of NSCL/P in a sample of the Iranian population.     

Meta-Analysis of Associations Between Interleukin-10 Polymorphisms and Susceptibility to Vasculitis

Objective: This study determined whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to vasculitis.

Methods: A meta-analysis was conducted of the associations between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and vasculitis.

Results: A total of 21 comparative studies involving 4121 patients and 5504 controls were considered in the meta-analysis. Meta-analysis revealed no association between the IL-10-1082 G allele and vasculitis in all study subjects (OR?=?0.927, 95% CI?=?0.780–1.102, p?=?0.389). However, disease-specific meta-analysis showed an association between Wegener’s granulomatosis (WG) and the IL-10-1082 G allele (OR?=?0.729, 95% CI?=?0.547–0.971, p?=?0.031). Meta-analysis revealed an association between vasculitis and the IL-10-819 C allele (OR?=?0.804, 95% CI?=?0.706–0.916, p?=?0.001) in all study subjects and Behcet’s disease (BD) (OR?=?0.724, 95% CI?=?0.679–0.781, p?<?1.0?×?10^?9). Meta-analysis of the IL-10-592 C allele showed an association with vasculitis in all study subjects (OR?=?0.805, 95% CI?=?0.619–0.938, p?=?0.005) and BD (OR?=?0.718, 95% CI?=?0.661–0.781, p?<?1.0?×?10^?9). Meta-analysis of the IL-10 haplotype revealed an association between the GCC haplotype and vasculitis in Europeans (OR?=?1.239, 95% CI?=?1.105–1.513, p?=?0.035).

Conclusions: This meta-analysis showed that IL-10 polymorphisms are associated with vasculitis susceptibility, especially in WG and BD.     

IL‐12B and IL‐10 gene polymorphisms in the development of Hashimoto's thyroiditis

Functional genetic polymorphisms that altered gene expression of cytokines are candidate genetic factors that could modulate the development and progression of Hashimoto's thyroiditis (HT). IL‐12B gene encoded the IL‐12p40 subunit, which is included in the pro‐inflammatory heterodimeric cytokines IL‐12p70 and IL‐23. IL‐10 is an important Treg cytokine suppressing inflammatory cytokine production and autoimmunity. This study was designed to compare ?1082A/GIL‐10 and +1188A/C3′UTRIL‐12B genotype distribution in 130 patients with HT to a group of 157 healthy controls in attempts to determine an association with HT development. Genotyping for the 3′UTRA/C IL‐12B polymorphism was performed using RFLP‐PCR and genotyping for ?1082A/G IL‐10 by ARMS‐PCR assay. Patients with HT were divided into euthyroid and hypothyroid stages. There were no significant differences in the genotype and allele frequencies of the IL‐12B polymorphism between patients with HT and controls. We observed higher euthyroid HT risk for individuals with CC genotype, unlike to develop hypothyroidism with OR = 1.68. Regarding the polymorphism rs1800896, it was shown the significantly higher frequency of homozygous genotype GG in cases vs controls (OR = 2.19; P = 0.024). Moreover, the combination of genotype AA of 3′UTRIL‐12B with GG of ?1082IL‐10 was associated with a threefold increasing risk (OR = 3.188; P = 0.022) of developing HT compared to individuals with the presence of 3′UTR allele C (AC+CC) simultaneously with AA genotype of ?1082IL‐10. Our data raise the possibility that the combined effect of polymorphisms from proinflammatory and anti‐inflammatory cytokines may be more decisive to HT development.     

Association between interferon lambda 3 rs12979860 polymorphism and clinical outcome in dengue virus‐infected children

Single nucleotide polymorphisms (SNPs) in immune‐related genes have been shown to play a role in driving the development of the severe phenotypes of dengue virus (DENV) infection. We assessed the association between IFNL3 gene SNP (rs12979860) and dengue clinical outcomes in children. Patients with dengue‐related symptoms (aged 1–15 years) admitted at a public hospital in Northeast Brazil were invited to participate. The association between rs12979860 polymorphism and dengue classification and clinical signs and symptoms were analysed. A total of 206 DENV‐infected children were included: 53.4% of the infections were classified as severe dengue. The T allele carriers had higher risk of developing severe dengue when compared to CC genotype carriers (OR: 1.81; 95% CI: 0.98–3.32 p = .054). The T allele carriers also showed longer fever episodes when compared to patients with the CC genotype (OR: 1.90; 95%CI: 1.07–3.38; p = .027). On the other hand, the ones carrying the CT/TT genotype had 70% lower chance of developing thrombocytopenia when compared to those with the CC genotype (OR: 0.30; 95%CI: 0.08–0.88; p = .042). Our findings demonstrated that the T allele carriers of the IFNL3 gene had higher risk of developing severe dengue, suggesting a link between IFN‐λ expression and DENV immunopathogenesis.     

白细胞介素10基因启动子区多态性与乙型肝炎病毒感染预后的关联研究

目的探讨中国汉族人白细胞介素10基因(interleukin10gene,IL10)启动子区单核苷酸多态性与乙型肝炎病毒(hepatitisBvirus,HBV)感染、转归的关联。方法采用聚合酶链反应-限制性片段长度多态性分析方法,检测231例HBV感染者,165例HBV感染康复者和135名正常对照者IL10基因启动子-1082G/A、-819T/C、-592A/C位点基因型。结果IL10基因启动子-1082G/A、-819T/C、-592A/C位点基因型和等位基因在HBV感染组、HBV感染康复组和正常对照组之间的分布频率比较差异无统计学意义(P>0.05),在血清HBV-DNA<1×103拷贝/mL的HBV感染者组和HBV-DNA≥1×103拷贝/mL组之间的分布频率比较差异亦无统计学意义(P>0.05);但IL10基因启动子-819T/C和-592A/C位点基因型和等位基因在HBV无症状携带组和慢性乙型肝炎组之间的分布差异有统计学意义(P<0.05),-819T/C位点TT型和-592A/C位点AA型在慢性乙型肝炎组的频率明显较高。结论汉族人IL10基因启动子多态性可能与人群对HBV易感性及感染后的病毒血症水平无显著相关性;但IL10启动子-819T/C和-592A/C位点基因多态性与HBV感染后的肝脏炎症反应有关。     

Genetic variant of IL28B rs12979860, as predictive marker of interferon‐based therapy in Pakistani population

Hepatitis C virus (HCV) genotypes and genetic variants of interleukin 28B (IL28B) are significantly associated with interferon plus ribavirin treatment of HCV infection. We investigated the distribution of HCV genotypes and single‐nucleotide polymorphisms (SNPs) of IL28B (rs12979860 and rs8099917) in Pakistani population. IL28B genotyping was performed by allele‐specific PCR and restriction fragment length polymorphism PCR in 140 chronic hepatitis C patients (CHC) and 120 healthy controls. HCV genotype 3 (HCVG3) was the most prevalent genotype, 71.4% (n = 100/140) and with the highest treatment response of 90% (n = 90/100). The overall treatment response of all the HCV genotypes was 82% (n = 115/140). The distribution of IL28B rs12979860CC genotype in treatment responder and non‐responder groups was 40.8% (n = 47/115) and 16% (n = 4/25) respectively. IL28B rs12979860CC genotype demonstrated a significant correlation (p = 0.019) with interferon‐based therapy of HCV infection. However, there was no observed association of IL28B rs8099917 polymorphism with treatment response in CHC patients (p = 0.264). In conclusion, HCV genotypes and IL28B rs12979860 are predictive markers for the efficiency of interferon plus ribavirin combinational therapy of HCV infection. We recommend the inclusion of testing for these markers in the clinical criteria for decision making for HCV therapy in Pakistani population.     

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.     

Association of interleukin‐10 promoter region polymorphisms with risk factors of Atherosclerosis

Atherosclerosis is considered as an inflammatory disease, and carotid artery intima‐media thickness (IMT) and carotid plaque are generally used as intermediated phenotype of atherosclerosis. The aim of this study was to investigate whether carotid IMT and plaque are associated with promoter region polymorphisms of interleukin 10 (IL‐10) gene. We recruited 135 subjects from a rural area of south‐eastern part of South Korea. Three polymorphisms in the promoter region of IL‐10 (?1082 A/G, ?819 T/C and ?592 A/C) were genotyped by pyrosequencing. Carotid IMT was measured at common carotid arteries, and carotid bulbs and cardiovascular risk factors such as cholesterol, blood pressure, uric acid and homocysteine were measured using blood samples. Subjects with the minor allele (C) of ?819 T/C or the minor allele (C) of ?592A/C showed lower values in carotid IMT than those with major allele homozygote of each polymorphism (P = 0.018 and P = 0.031, respectively). Subjects with carotid plaque were significantly older and showed higher values in carotid IMT, uric acid and homocysteine than those without plaque (P < 0.01, respectively). In conclusion, the promoter region polymorphisms of IL‐10 gene associate with carotid IMT and plaque. Further studies with larger samples are needed to provide stronger evidence to justify anti‐atheromatous properties of IL‐10.