Interleukin-10 promoter polymorphisms associated with susceptibility to lumbar disc degeneration in a Chinese cohort

We investigated a possible association between interleukin (IL)-10 single nucleotide polymorphisms (SNPs) and susceptibility to and severity of lumbar disc degeneration (LDD) in a Chinese cohort of 320 patients with LDD and 269 gender- and age-matched controls. The degree of disc degeneration was determined by magnetic resonance imaging using Schneiderman's classification. Genetic analysis of IL-10 promoter polymorphisms (at -1082 A/G, -819 T/C, and -592 A/C) was carried out by PCR-RFLP. A total of 134 herniated lumbar intervertebral discs were collected during surgery for IL-10 mRNA detection. For SNPs at -592, the A allele and AA genotype frequencies were significantly higher in LDD patients than in controls. Similarly, the AA genotype and A allele frequencies at -1082 were significantly higher in cases than in controls. Among the LDD subjects, carriers of AA at -592 and GG at -1082 had significantly lower mean IL-10 mRNA expression than the other two genotypes. The SNPs at each locus were not significantly associated with severity grade in the LDD patients. Logistic regression analyses showed that the AA at -1082, AA at -592, and IL-10 mRNA expression level were independent risk factors for LDD. We conclude that the IL-10 SNPs at -1082 A/G and -592 A/C as well as IL-10 mRNA in the herniated lumbar intervertebral discs are associated with susceptibility to LDD in this Chinese cohort, but not with disease severity.     

EB病毒感染及XRCC1、IL-10基因多态性与甲状腺癌的关联性分析

摘要 目的：探究Epstein-Barr病毒（EB病毒）感染及X射线交错互补修复因子1（XRCC1）、白介素-10（IL-10）基因多态性与甲状腺癌的关联性。方法：选取2020年1月~2022年12月132例甲状腺癌患者为研究组以及同期132例甲状腺良性腺瘤患者为对照组,采用原位杂交技术检测肿瘤标本EB病毒感染情况,聚合酶链反应-限制性内切酶片段长度多态性法检测XRCC1-399G/A位点、IL-10-592C/A位点基因多态性。结果：研究组EB病毒感染阳性率55.3%,高于对照组的33.3%（P<0.05）。研究组XRCC1-399G/A位点GA、AA基因型及A等位基因频率均高于对照组（P<0.05）;两组IL-10-592C/A各基因型频率比较差异无统计学意义,但研究组A等位基因频率高于对照组（P<0.05）。EB病毒感染阳性者较阴性者甲状腺癌风险增加3.337倍（95%CI：1.272~8.752）,携带XRCC1-399位点（GA+AA）型者较GG型风险增加2.438倍（95%CI：1.223~4.859）,携带IL-10-592位点（CA+AA）型者较CC型未增加甲状腺癌风险。不同病理类型甲状腺癌患者EB病毒感染情况及XRCC1-399位点、IL-10-592位点基因型分布比较差异均无统计学意义。结论：EB病毒感染阳性、XRCC1-399G/A位点突变基因型可能是甲状腺癌发病的易感因素,但二者与甲状腺癌病理类型无明显关系,而IL-10-592C/A基因多态性可能与甲状腺癌无关。     

Interleukin-1B (-511) gene polymorphism is associated with acute coronary syndrome in the Turkish population

Objectives: acute coronary syndrome (ACS) is defined as an inflammatory disease associated with development of atherosclerosis and instability. IL-1 is a candidate inflammatory cytokine that is thought to trigger ACS. The purpose of this study was to determine the relationship between IL-1 gene family polymorphisms (IL-1RN, IL-1B in positions -511 and +3953) and ACS in the Turkish population. Methods: a total of 381 people participated in the study, with 117 control subjects and 264 ACS patients. Of the 264 ACS patients, 112 were diagnosed with stable angina pectoris (SAP) and 152 were diagnosed with unstable angina pectoris (USAP). The polymerase chain reaction (PCR) was used to determine the genotype of IL-1RN. The genotypes of IL-1B (-511 and +3953) were determined by PCR, followed by restriction enzyme digestion of the PCR products. Results: there were no significant differences in both IL-1RN, IL-1B (-511 and +3953) genotype distributions and IL-1RN allele frequencies between ACS patients and the control subjects. In addition, no association was observed in the allele frequency of IL-1B (-511 and +3953) between ACS patients and controls (p = 0.113 and p = 0.859, respectively), or between SAP patients and controls (p = 0.575 and p = 0.359, respectively). However, IL-1B allele 1 (C) (-511) polymorphism in USAP patients was found to be significantly different from that of control subjects (p = 0.041, OR: 2.01; 95% CI: 1.985-3.933). A significant difference was also observed between USAP and SAP patients for IL-1B (+3953) allele 1 (C) polymorphism; (p = 0.043, OR: 1.522; 95% CI: 1.012-2.88). Conclusion: these results show that IL-1RN gene polymorphism has no association with ACS. However, the allele 1 (C) of IL-1B (-511) may be a risk factor for susceptibility to USAP in the Turkish population.     

Interleukin-8 and -10 gene polymorphisms in irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diagnoses seen by primary care providers and gastroenterologists. Proinflammatory cytokines interleukin (IL)-6 and IL-8 have been found increased in IBS patients. Cytokine gene single nucleotide polymorphisms (SNPs) of IL-8 and IL-10 have not been assessed in Mexican IBS patients. DNA was extracted from peripheral blood leucocytes of 45 IBS unrelated patients and 137 controls. Allele, genotype, and haplotype frequencies were determined by analyzing SNPs of IL-8 and IL-10 genes. IL-8 + 396 G allele (P = 0.02), IL-8 + 396(G/G) and IL-8 + 781(C/T) genotypes (P < 0.001), IL-10 - 1082A allele and IL-10 - 1082(A/A) genotype (P < 0.001) were significantly increased in the IBS group. Haplotypes IL-8 ATCC (P = 0.03) and IL-10 ACC (P < 0.001) were associated with susceptibility to develop IBS. An association of certain polymorphisms of IL-8 and IL-10 in IBS patients compared to controls was demonstrated, suggesting a role of these cytokine SNPs in the pathophysiology of IBS.     

Interleukin-10 gene polymorphisms and chronic/aggressive periodontitis susceptibility: A meta-analysis based on 14 case-control studies

Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and IL-10 gene polymorphisms was associated with altered interleukin-10 levels, therefore, we aimed to conduct a meta-analysis assessing the association of IL-10 genetic polymorphisms with the risk of both chronic periodontitis (CP) and aggressive periodontitis (AgP). Electronic databases were acquired from PubMed, Embase, the Sinomed and WANFANG. Fourteen studies with 1438 patients and 1303 control subjects investigated the association of the three single-nucleotide polymorphisms (SNPs) of IL-10 (-1082A>G, -819C>T, -592C>A) and chronic/aggressive periodontitis risk were brought into this study. We found that there was no association between IL-10 -1082 gene polymorphism and periodontitis risk (either CP or AgP), even when we separately investigated sub-group analysis among Caucasians. The -819 polymorphism seemed to be a genetic risk factor to CP among Caucasians (T allele vs. C allele: OR=1.55, 95%CI=1.07-2.24; CT vs. CC: OR=1.64, 95%CI=1.00-2.67). When excluding one study deviated from HWE, the results showed that the T allele carriers had a significantly risk of CP in overall population (T allele vs. C allele: OR=1.23, 95%CI=1.03-1.48). Furthermore, the results of this meta-analysis showed that -592 polymorphism was associated with a significantly increased risk of CP (A allele vs. C allele: OR=1.38, 95%CI=1.04-1.85; AA vs. CA+CC: OR=1.39, 95%CI=1.05-1.85 for overall analysis; A allele vs. C allele: OR=1.97, 95%CI=1.36-3.86; AA vs. CC: OR=3.70, 95%CI=1.32-10.39; CA vs. CC: OR=2.22, 95%CI=1.36-3.64, AA+CA vs. CC: OR=2.35, 95%CI=1.46-3.79 for Caucasian descent analysis). This meta-analysis suggested that IL-10 -819 and -592 gene polymorphisms were associated with CP, especially among Caucasians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on periodontal disease..     

Association of TNF-α and IL-10 polymorphisms with tuberculosis in Tunisian populations

Cytokine Th1/Th2 balance is known to play a key role in controlling Mycobacterium tuberculosis infection. Based upon the functional role of the TNF-α [-308 G(low)?→?A(high) (rs1800629)] and IL-10 [-1082 A(low)?→?G(high) (rs1800870), -819 T(low)?→?C(high) (rs1800871) and -592 A(low)?→?C(high) (rs1800872)] single nucleotide polymorphisms (SNPs) on production levels, we genotyped 76 patients with pulmonary tuberculosis (TB) (pTB), 55 patients with extrapulmonary TB (epTB) and 95 healthy blood donors by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that -308 A allele was associated with increased risk susceptibility to epTB (OR?=?1.96; 95% CI, 1.04-3.71; P?=?0.024). The -1082 AG genotype was significantly associated with increased risk development of epTB (odds ratio [OR]?=?3.69; 95% confidence intervals [CI], 1.73-7.92; P corrected for the number of genotypes [Pc]?=?0.0003). By contrast, -1082 AA genotype appeared to be associated with resistance to pTB (OR?=?0.38; 95% CI, 0.19-0.74; Pc?=?0.006) and epTB (OR?=?0.22; 95% CI, 0.1-0.48; Pc?=?0.00006). High-producer IL-10 GCC haplotype seemed to be associated with 2.11-fold (95% CI, 1.28-3.46; Pc?=?0.003) and 2.57-fold (95% CI, 1.5-4.4; Pc?=?0.0006) increased susceptibility to pTB and epTB, respectively. Combination of TNF-α/IL-10 high producer genotypes was associated with increased 3.13-fold (95% CI, 1.23-8.05; Pc?=?0.028) susceptibility to epTB. However, combined TNF-α/IL-10 low producer genotypes appeared to have protect effect to pTB (OR?=?0.44, 95% CI, 0.21-0.89; Pc?=?0.04) and epTB (OR?=?0.26, 95% CI, 0.1-0.62; Pc?=?0.0028). Collectively, our results showed that analysed SNPs in the TNF-α and IL-10 gene polymorphisms play key role in susceptibility to or protection against TB development in Tunisian populations.     

Association of TP53 gene codon 72 polymorphism with endometriosis in Mexican women

The TP53 tumor suppressor gene plays an important role in cell cycle regulation; polymorphisms of this gene have been associated with endometriosis. We examined the role of TP53 codon 72 polymorphism by comparing genotypes of 235 healthy Mexican women (controls with surgically excluded endometriosis) with the genotypes of 151 Mexican women with endometriosis. The observed genotype frequencies for controls and endometriosis patients were 8 and 22% for proline/proline (Pro/Pro), 30 and 34% for proline/arginine (Pro/Arg), and 62 and 44% for arginine/arginine (Arg/Arg), respectively. We found that odds ratio (OR) = 3.3; 95% confidence intervals (95%CI) = 1.7-6.4; P = 0.0001. The association was also evident in the comparison of the distributions of genotypes Pro/Pro and Pro/Arg in patients with moderate-to-severe endometriosis; OR = 1.9; 95%CI = 0.95-3.9; P = 0.049. We suggest that genotype Pro/Pro of codon 72 polymorphism in TP53 contributes significantly to endometriosis susceptibility in the Mexican population.     

Interleukin-10-1082 gene polymorphism is associated with papillary thyroid cancer

The etiopathogenesis of thyroid cancer has not been clearly elucidated although the role of chronical inflammation and the imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. The aim of the present study was to investigate whether cytokine gene polymorphisms are associated with papillary thyroid cancer (PTC), and to evaluate the relationship between genotypes and clinical/laboratory manifestation of PTC. Tumor necrosis factorα (TNFα) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 A-1082G (rs 1800896) single nucleotide polymorphisms in DNA from peripheral blood leukocytes of 190 patients with thyroid cancer and 216 healthy controls were investigated by real-time PCR combined with melting curve analysis. There was no notable risk for PTC afflicted by TNFα-308 and IL-6-174 alone. However, IL-10-1082 G allele frequency were higher among PTC patients than healthy controls (p = 0.009). The patients with IL-10-1082 GG geotype have twofold increased risk of developing thyroid cancer according to AA genotype (OR 2.07, 95 % CI 1.21–3.55). In addition, the concomitant presence of IL-10-1082 G allele (GG + AG genotypes) together with IL-6 -174 GG genotype has a nearly twofold increased risk for thyroid cancer (OR 1.75 with 95 % CI 1.00–3.05, p = 0.049). We suggest that IL-10-1082 G allele is associated with an increased risk of PTC. The polymorphism of IL-10 gene can improve our knowledge about the pathogenesis of PTC, and could provide to estimate people at the increased risk for PTC.     

The IL-8 gene polymorphisms and the risk of the hepatitis B virus/infected patients

Interleukin-8 (IL-8) belongs to the superfamily of CXC chemokines, contributing to human cancer progression through potential mitogenic, angiogenic, and motogenic functions. We hypothesize that the functional polymorphism of IL-8 may influence the inflammatory process during pathological stage from hepatitis to hepatocellular carcinoma (HCC). Two polymorphisms in the IL-8 gene (-251A/T and +781C/T) were examined in 160 cases of chronic hepatitis B, 80 cases of hepatitis B virus (HBV)-related liver cirrhosis (LC), 150 cases of HBV-related HCC, and 150 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. In the LC group, the AA genotypes were associated with a significantly decreased risk of LC compared with the TT genotype (OR=0.14, 95% CI 0.02-0.87, p=0.035). The data also revealed that subjects with the A allele appeared to have lower susceptibility to LC than those with the T allele (OR=0.48, 95% CI 0.25-0.92, p=0.027). The +781C/T polymorphism of IL-8 was not found relevant to the liver diseases. This study indicated that the IL-8 gene -251 AA genotype might be a protect factor for LC.     

Polymorphisms of IL-10 gene in patients infected with HCV under antiviral treatment in southern Brazil

Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Gene polymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group (p = 0.005 and p = 0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group (p < 0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis (p = 0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR).     

Interleukin-10 gene promoter polymorphisms and their protein production in pleural fluid in patients with tuberculosis

Associations of interleukin-10 (IL-10) gene promoter polymorphisms and pleural tuberculosis risk remain unclear. The objective of this study was to determine IL-10 gene promoter polymorphisms at -1082, -819 and -592 sites and their protein production in pleural fluid (PF) in patients with and without pleural tuberculosis. IL-10 gene promoter polymorphisms at the -1082, -819 and -592 sites were genotyped using a SNaPshot assay. Protein levels of IL-10 in PF were measured using an enzyme-linked immunosorbent assay. There were no significant differences in the genotype and allele frequencies of IL-10 gene promoter polymorphisms at position -1082 between the pleural tuberculosis and the control groups. However, the frequency of -819 T or -592 A alleles was significantly more common in patients with pleural tuberculosis than controls. The protein levels of IL-10 in PF were statistically higher in the pleural tuberculosis group than in the control group. Moreover, the polymorphisms at the -1082, -819 and -592 sites were associated with protein levels of IL-10 in PF in the pleural tuberculosis group, while in the control group, only the polymorphism at position -1082 correlated with the protein levels. These findings support the association between IL-10 promoter polymorphisms at -819 and -592 sites and their protein production with pleural tuberculosis risk.     

Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is one of the most common causes of inflammatory arthritis, with an estimated prevalence of 0.1-0.9%. Genetic factors have been strongly implicated in its aetiology, and heritability as assessed by twin studies has been estimated to be >90%. HLA- B27 is almost essential for inheritance of AS; it is not merely sufficient for explaining the pattern of familial recurrence of the disease. This study's purpose is to investigate the association of ankylosing spondylitis with single-nucleotide polymorphisms (SNPs) in the IL-1 family: IL-1a (-889C/T) rs1800587, IL-1b (-511C/T) rs16944, IL-1b (+3962C/T) rs1143634, IL-1R (Pst-1 1970C/T) rs2234650 and IL-1RA (Mspa-1 11100C/T) rs315952. 99 unrelated Iranian AS patients and 217 healthy control subjects were selected. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the polymorphisms were determined: The IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with AS. Genotype frequencies at IL1R rs2234650 differed between cases and controls (χ(2)=8.85; p=0.01); the IL1R rs2234650 C/T and T/T genotypes were less common in AS patients than controls. The IL1R rs2234650 C/T genotype was inversely associated with AS comparing with the IL1R rs2234650 C/C genotype (OR=0.48; p=0.005). IL1R rs2234650 C/T genotype was less common in patients than controls (OR=0.37; p=0.02).Furthermore IL1R rs2234650 T allele was strongly associated with HLA-B2702 patients rather than HLA-B2705 but was not associated with HLA-B27 negative patients (OR=0.33; p=0.01). Polymorphisms of IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with ankylosing spondylitis but inversely in this study IL1R rs2234650 was significantly associated and carriage of T allele in IL1R rs2234650 seems to be protective, while carriage of C allele result in two fold higher risk of developing AS.     

Association between promoter variants of interleukin-18 and schizophrenia in a Han Chinese population

An increasing amount of evidence suggests that interleukin-18 (IL-18) plays a pivotal role in the pathophysiology of schizophrenia. However, association between single nucleotide polymorphism of IL-18 and the risk of schizophrenia has not been clarified. This study examined whether two promoter polymorphisms -137 G/C (rs187238) and -607 C/A (rs1946518) of IL-18 were associated with schizophrenia and six clinical symptoms (disorder of perception, thought disorder, disturbance of emotion, disorder of behavior and volition, suicide action, and aggressive action) to provide data for screening high-risk Han Chinese individuals. Three hundred seventy-two schizophrenic patients and 353 healthy controls from a Han Chinese population were examined to assess their genotype and allele frequencies of the two promoter polymorphisms of IL-18. The genotype distributions in both patients and controls were within Hardy-Weinberg equilibrium. No significant differences were observed in the genotype or the allele frequencies of the two single-nucleotide polymorphisms between patients and controls. However, genotype frequencies of -607 C/A showed significant differences between patients and controls in the appearance of perception disorder (χ2 = 6.153, p = 0.046). A significant difference was detected in -137 G/C between patients and controls in the appearance of aggressive action (χ2 = 3.909, p = 0.048). In conclusion, IL-18 gene promoter polymorphisms may not contribute to the susceptibility of schizophrenia in a Han Chinese population, but two single-nucleotide polymorphisms, -137 G/C and -607 C/A, may play a role in the development of perception disorder and aggressive action, respectively.     

Cytokine gene polymorphisms and cytokine levels in pulmonary tuberculosis

Polymorphisms in the cytokine genes are known to influence cytokine levels and may be associated with outcome of infections. We investigated the polymorphisms in the cytokine genes namely IFN-gamma (+874 and +5644), IL-2 (-330 and +160), IL-4 (VNTR), IL-6 (-174), IL-10 (-1082 and -819) and IL-12B (+1188) in 188 normal healthy subjects (NHS) and 166 pulmonary tuberculosis patients (PTB) using polymerase chain reaction-based methods. To study the influence of cytokine gene polymorphisms on cytokine levels, phytohaemagglutinin and culture filtrate antigen of Mycobacterium tuberculosis-induced cytokine levels were measured by ELISA from 72-h-old peripheral blood mononuclear cell culture supernatants. Significantly decreased frequency of TT genotype of IL-2 -330 polymorphism (p=0.024, odds ratio (OR) 0.53, 95% CI 0.31-0.92) was observed in patients compared to NHS. The genotype frequencies of other polymorphisms were not different between patients and NHS. IL-12p40 levels were significantly decreased among NHS with AA genotype of IL-12B gene polymorphism compared to NHS with AC genotype (p<0.05). Increased levels of IL-12p40 were observed among patients with CC genotype of IL-12B gene compared to patients with other genotypes (p<0.01). The present study suggests that the TT genotype of IL-2 -330 polymorphism may be associated with the protection to PTB in south India. Further, +1188 polymorphism of IL-12B gene either alone or in combination with closely linked genes may regulate IL-12p40 production and may play a major role on acquired immunity to tuberculosis.     

Relationship between single nucleotide polymorphism of interleukin-18 and susceptibility to pulmonary tuberculosis in the Chinese Han population

Interleukin-18 (IL-18) is a multi-functional cytokine capable of inducing either Th1 or Th2 polarization depending on the immunologic milieu. IL-18 may influence the host response to Mycobacterium tuberculosis (M.tb) infection. To investigate the relationship between single nucleotide polymorphisms of the IL-18 and susceptibility to pulmonary tuberculosis in the Chinese Han population, the IL-18 gene was sequenced to detect polymorphisms and to examine the genotype frequencies in 300 patients and 702 healthy controls. DNA sequencing revealed three IL-18 variants: rs1946518, rs5744247, and rs549908. It also revealed that allele A of rs1946518 confers a 1.47-fold increased risk of developing tuberculosis (TB) (P = 0.0001, OR [95%CI] = 1.47 [1.21-1.78]), and that the C allele of rs5744247 confers a 0.77-fold decreased risk of disease (P = 0.01, R [95%CI] = 0.77 [0.632-0.937]). The genotypes rs1946518, rs5744247 and rs549908 were found to be significantly associated with TB. Estimation of the frequencies of haplotypes revealed a potential risk haplotype AGA (P = 0.01, OR [95%CI] = 1.41 [1.15-1.72]) and a protective haplotype CCA (P = 0.01, OR [95%CI] = 0.70 [0.57-0.85]) for TB. The present findings suggest that polymorphisms in the IL-18 gene may affect susceptibility to TB and increase the risk of developing the disease in the Chinese Han population.     

Associations between interleukin-10 polymorphisms and susceptibility to juvenile idiopathic arthritis: a systematic review and meta-analysis

Background

Cytokine genes, including interleukin-10 (IL-10), are known to play important roles in the pathogenesis of juvenile idiopathic arthritis (JIA). This study aims to determine whether the IL-10 polymorphisms confer susceptibility to JIA.

Methods

A meta-analysis was performed on the associations between the IL-10-1082 G/A, -592 C/A, and -819 C/T polymorphisms and JIA. A total number of 7 studies involving 1,785 patients and 6,142 controls were considered in the meta-analysis.

Results

Meta-analysis of the IL-10-592 C/A and -819 C/T polymorphisms showed no association with JIA in the study participants, or in Caucasian or Middle Eastern participants. Meta-analysis of the IL-10-1082 A allele in all study participants, Caucasian and Middle Eastern, showed significant associations with RA (overall ORs were 1.17, 1.15, and 1.41, respectively). Meta-analysis of the AA versus GG genotype of the IL-10-1082 G/A polymorphism revealed significant associations with JIA (OR = 3.66, 95% CI = 1.44-9.29, P = 0.006) in participants from Middle Eastern countries. Additionally, meta-analysis of the GG versus AA+GA genotypes of the IL-10 -1082 G/A polymorphism revealed the GG genotype as the protective factor against JIA in the Middle Eastern subgroup (OR = 0.44, 95% CI = 0.20-0.94, P = 0,04). Moreover, meta-analysis of the IL-10 -1082 A allele in 4 studies on Hardy-Weinberg equilibrium showed a significant association with JIA (OR = 1.17, 95% CI = 1.07-1.28, P = 0.0009). No association was found between the IL-10 (-1082, -819, -592) ACC, ATA, and GCC haplotypes and JIA.

Conclusions

These results suggest that the IL-10-1082 G/A polymorphism confers susceptibility to JIA.

     

Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection

The natural outcome and response to treatment in hepatitis C virus (HCV) infection varies between individuals. Whereas some variation may be attributable to viral and environmental variables, it is probable that host genetic background also plays a significant role. Interleukin (IL)-10 has a key function in the regulation of cellular immune responses and in the suppression of pro-inflammatory cytokine secretion. Functional polymorphisms in the IL-10 gene have been described. We investigated the role of these polymorphisms in the outcome of HCV infection, treatment response and development of fibrosis in a case-control association study. Self-limiting infection was associated with the IL-10 (–592) AA genotype (OR=2.05; P=0.028). Persistent infection was associated with the IL-10 (–1082) GG genotype (OR=0.48; P=0.018). Sustained response to interferon therapy was associated with the IL-10 (–1082) GG genotype (OR=2.28; P=0.005) and the haplotype GCC (OR=2.27; P=0.020). The IL-10 (–1082) AA genotype and the ATA/ATA and ACC/ACC homozygous haplotypes were more frequent among patients with rapid fibrosis. Furthermore, the microsatellites IL-10.R and IL-10.G were associated with interferon response with IL-10R.2 conveying susceptibility (OR=1.80; P=0.034), and IL-10R.3 and IL-10.G13 being protective (OR=0.47; P=0.003 and OR=0.59; P=0.042, respectively). We conclude that polymorphisms in the IL-10 promoter appear to have some influence on the outcome of HCV infection, treatment and development of fibrosis.Susanne Knapp and Branwen Hennig contributed equally to this study     

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristics of two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restricted fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype (P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).     

Interleukin-10 and interleukin-18 promoter polymorphisms in an Italian cohort of patients with undifferentiated carcinoma of nasopharyngeal type

Purpose: Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV). Methods: Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions –1082, −819, −592 by direct sequencing and IL-18 gene at position −607 and −137 by allele –specific PCR. EBV DNA serum viremia was evaluated by QC-PCR. Results: The distributions of the IL-10 and IL-18 genetic variants were not different between UCNT patients and healthy controls. The frequency of IL-10 –1082G allele, which is associated with high IL-10 expression, showed a nearly statistically significant increase in UCNT patients EBV DNA-negative as compared to healthy controls (OR=3.3 95% CI: 1.2–9.8). Subjects with C/C or C/G combined IL-18 genotypes showed an increased risk of being with Stages III-IV (OR=2.1 95% CI: 1.2–6.6). Conclusion: This study was performed to improve the definition of the pathogenetic factors implicated in UCNT by addressing the correlation between cytokine polymorphisms and clinical parameters. This is the first study investigating the possible role of the IL-18 and IL-10 polymorphisms in the development and outcome of UCNT. In our genetic analysis there is no evidence for involvement of IL-10 promoter polymorphisms alone in the genetic predisposition to this tumor. On the other hand, IL18 genetic variants may represent a genetic risk factor for tumor aggressiveness.     

Association Study of IL-12B Polymorphisms Susceptibility with Ankylosing Spondylitis in Mainland Han Population

Objective

This study aims to determine whether the genetic polymorphisms of IL-12B gene is a susceptibility factor to Ankylosing spondylitis (AS) in mainland Han Chinese population.

Method

Eight single-nucleotide polymorphisms (SNPs) (rs10045431, rs11167764, rs3212227, rs6556412, rs6556416, rs6871626, rs6887695 and rs7709212) in the IL-12B gene were genotyped by iMLDR Assay technology in 400 patients [96% (384/400) HLA-B27(+)] and 395 geographically and ethnically matched healthy controls in mainland Han Chinese population. The correlation between IL-12B genetic polymorphisms and AS activity index (BASDAI, BASFI) were tested.

Results

The significant difference was found in genotype distribution between AS and healthy controls (χ² = 6.942, P-value = 0.031) of the SNP rs6871626. Furthermore, significant evidence was also detected under the recessive model for minor allele A. The AA genotype carrier had 1.830 fold risk compared with C allele carrier (with CC and AC genotypes) [OR (95% CI) = 1.830 (1.131-2.961), P-value = 0.014]. Nevertheless, the difference was no longer significant after Bonferroni correction. Subset analysis on cases with HLA-B27(+) did find the same results. Three genotypic groups (AA, CC and CA) in rs6871626 site was highly associated with the BASDAI and BASFI (P-value = 0.012 and P-value = 0.023, respectively), after adjustment for effect of age, sex, and disease duration, the P-value was 0.031 and 0.041, respectively. The AA genotype of rs6871626 was also significantly correlated with an increased BASDAI and BASFI compared to the AC and CC genotypes in AS patients.

Conclusion

Our findings suggest that rs6871626 may be associated AS susceptibility and with disease activity (BASDAI, BASFI) in mainland Han Chinese population.