Single nucleotide polymorphism and haplotype association of the interleukin-8 gene with nasopharyngeal carcinoma

The cytokine interleukin-8 (IL-8) may play a role in the pathogenesis of nasopharyngeal carcinoma (NPC) through the modulation of tumor immune response or enhanced angiogenesis. Polymorphism of IL-8 gene, which may affect the production level of cytokine, has been inversely associated with a number of cancers. To test this hypothesis, we investigated the relationship of IL-8 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL-8 gene -845 T/C, -738 T/A, -353 A/T, -251 A/T and +678 T/C in 280 patients with NPC and 290 age and sex matched controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence specific primers method (PCR-SSP). There were significant differences in the genotype and allele distribution of -251 A/T polymorphism of the IL-8 gene among cases and controls. The -251 AA and AT genotypes were associated with a significantly increased risk of NPC as compared with the -251 TT genotypes (OR=1.820, 95% CI, 1.120-2.959, P=0.015 and OR=1.590, 95% CI, 1.104-2.290, P=0.013, respectively). Haplotype analysis revealed that the homozygosity of the AAT haplotype (defined by SNPs at positions -353, -251 and +678) of IL-8 gene conveys the highest risk for NPC compared with the homozygosity for the TTC haplotype (OR=1.396; 95% CI, 1.064-1.831; P=0.016). The -251 A/T polymorphism of IL-8 and its haplotype are associated with NPC in a Chinese population. Our data suggests that IL-8 gene may play a role in the development of NPC.     

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.     

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.     

Association between interleukin-10 gene -592 C/A polymorphism and the risk of type 2 diabetes mellitus: A meta-analysis of 5320 subjects

Increasing evidence suggests that interleukin-10 (IL-10) gene -592 C/A polymorphism may be associated with an increased risk of type 2 diabetes mellitus (T2DM). To provide a quantitative assessment of the association between this variant and risk of T2DM, we performed this meta-analysis. Systematic searches of electronic databases PubMed, Embase, Web of Science, CBMdisc and CNKI, as well as hand searching of the references of identified articles were performed. A total of 2698 T2DM cases and 2622 controls in seven case-control studies were included in this meta-analysis. The results showed no evidence for significant association between IL-10 gene -592 C/A polymorphism and T2DM risk (for A allele vs. C allele: OR=0.94, 95% CI=0.69-1.29, p=0.69; for A/A vs. C/C: OR=0.88, 95% CI=0.39-1.98, p=0.75; for A/A vs. A/C+C/C: OR=1.04, 95% CI=0.59-1.82, p=0.89; for A/A+A/C vs. C/C: OR=1.11, 95% CI=0.73-1.69, p=0.61). In addition, the similar results were obtained in the subgroup analysis based on the ethnicity. In summary, results from this meta-analysis suggest that the IL-10 gene -592 C/A polymorphism is not associated with T2DM risk.     

Association of variants in the BAT1-NFKBIL1-LTA genomic region with protection against myocardial infarction in Europeans

Single-nucleotide polymorphisms within the BAT1-NFKBIL1-LTA genomic region (6p21.3) and the LGALS2 gene (22q13.1), encoding a regulator for lymphotoxin-alpha, the product of the LTA gene, have been reported to be linked with the risk of myocardial infarction in Japanese. We employed nine polymorphisms from the BAT1-NFKBIL1-LTA region and one polymorphism from the LGALS2 gene, and investigated whether such associations were also present in Europeans. The study included 3657 patients with myocardial infarction and 1211 control individuals with angiographically normal coronary arteries. Minor homozygous genotypes of polymorphisms in BAT1 (rs2239527, -23C/G), NFKBIL1 (rs2071592, -63T/A) and LTA (rs1800683, -162G/A; rs909253, 252G/A; rs1041981, Thr26Asn) were associated with moderately protective effects against myocardial infarction (P 相似文献   

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.     

The synergistic effect of FC gamma receptor IIa and interleukin-10 genes on the risk to develop systemic lupus erythematosus in Thai population

Several linkage analyses have consistently shown that systemic lupus erythematosus (SLE) susceptible genes are located on chromosome 1q21-44. In this study, two major candidate genes, interleukin-10 (IL-10) and Fc gamma receptor IIa (FcgammaRIIa), within these regions were investigated in Thai SLE patients. The genotyping of three single-nucleotide polymorphisms (promoter area: -1082, -819 and -592) within IL-10 gene and one polymorphism (change amino acid at position 131) within FcgammaRIIa gene was determined in 195 SLE patients and 159 ethnically matched controls. The RR/RH genotypes of FcgammaRIIa were found to be significantly increased in SLE patients compared with healthy controls [OR = 2.01, 95% confidence interval (CI) = 1.28-3.14, P= 0.001]. Interestingly, the synergistic effect between RR/RH genotypes of FcgammaRIIa and ACC/ACC haplotype of IL-10 in susceptibility to SLE was observed (OR = 7.84, 95% CI = 1.60-52.04, P= 0.002). In addition, the FcgammaRIIa, RR homozygotes was also strongly associated with anticardiolipin antibody production (OR = 6.09, 95% CI = 1.38-30.54, P= 0.006). The result demonstrated that ACC haplotype of IL-10 gene and FcgammaRIIa R131 polymorphism can be used as marker for genetic susceptibility and severity to SLE in Thai population, particularly individuals carrying both specific genotypes.     

IL-10 promoter genetic polymorphisms and risk of Kawasaki disease in Taiwan

Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (-1082, -819, and -592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci -819 T > C and -592 A > C for KD cases was observed (P permutation = 0.029 and P permutation = 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p = 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090-2.443; P permutation = 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. The haplotype CC (-819, -592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987-1.797; p = 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant, p =0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and -592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.     

TIM3 gene polymorphisms in patients with chronic hepatitis B virus infection: impact on disease susceptibility and hepatocellular carcinoma traits

Hepatitis B virus (HBV) infection is associated with the development of acute and chronic liver diseases including hepatocellular carcinoma (HCC). T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3), which negatively regulates T-cell response and mediates phagocytosis of apoptotic cells, has been implicated in HBV infection and cancers. This study explored the polymorphisms of TIM3 gene in 535 patients with HBV-related liver diseases including 213 chronic hepatitis, 178 cirrhosis and 144 HCC, 72 HBV infection resolvers and 182 healthy controls and analyzed the effects of these polymorphisms on the disease susceptibility and HCC traits. TIM3-1541C/T, -1516G/T, -882C/T, -574G/T and +4259T/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Of the five polymorphisms genotyped, the allele T-containing genotypes (GT + TT), allele T and allele T-containing haplotype (CTCGT) of -1516G/T polymorphism were more frequent in HBV patients than in controls [P = 0.005, odds ratio (OR) = 2.300, 95% confidence interval (CI): 1.294-4.088; P = 0.004, OR = 2.266, 95% CI: 1.297-3.962; and P = 0.005, OR = 2.203, 95% CI: 1.260-3.854, respectively]. The allele T-containing genotypes and allele T of -1516G/T were associated with HCC tumor grade (P = 0.023 and P = 0.017, respectively) and lymph node metastasis (P = 0.024 and P = 0.017, respectively). These findings suggest that -1516G/T polymorphism in the promoter region of TIM3 gene may affect the disease susceptibility and HCC traits associated with HBV infection, potentially supporting the role of Tim-3 in T-cell dysfunction and exhaustion involved in persistent HBV infection and HCC development.     

白介素-23受体基因多态性与乙肝相关肝细胞癌的易感性研究

目的:探讨白介素-23受体(IL-23R)基因多态性与广西壮族人群乙肝相关肝细胞癌(HCC)易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对84例乙肝表面抗原(HBSAg)阳性HCC患者(病例组)和94例HbsAg阳性体检者(对照组)IL-23R基因rs10889677、rs1884444、rs114658173个位点的单核苷酸多态性进行检测及其部分标本进行直接测序鉴定。采用SHEsis软件构建IL-23R基因3个位点的单体型。Logistic回归分析IL-23R基因多态性和单体型与HCC遗传易感性的关系。结果:IL-23Rrs10889677、rs11465817位点的AA、AC、CC3种基因型和A、C两种等位基因在HCC组与对照组之间的分布差异无统计学意义(P>0.05)。rs1884444位点的TT、TG、GG三种基因型及T、G两种等位基因在病例组和对照组的频率分布差异均有统计学意义(P均<0.05),Logistic回归分析发现携带TG基因型的个体发生HCC的风险较携带TT基因型的个体增加(校正OR=2.20,95%CI=1.11～4.37)。单体型构建发现CGC、AGC、CTC、ATC、CGA、AGA、CTA、ATA等8种单倍体,病例组和对照组的AGC单倍体分布差异有统计学意义(P<0.05),AGC单倍体携带者发生HCC的风险明显增加(校正OR=2.71,95%CI=1.06～6.93)。结论:IL-23R基因rs1884444位点TG基因型可能是HCC发病的危险因子;乙肝背景下AGC单倍体携带者患HCC的风险增加2.71倍,可能是乙肝相关肝癌发病的危险因素。     

Association of interleukin-18 gene polymorphism (-607A/A genotype) with susceptibility to chronic hepatitis B virus infection

Polymorphisms in the gene promoter can lead to different levels of cytokine expression and let some individuals have unique immune responses. Therefore, the association of single nucleotide polymorphism of interleukin (IL)-18 promoter region in chronic hepatitis B virus (HBV) infection was examined. The results demonstrated the significant involvement of genotype A/A at position -607 in patients (n = 140) when compared with healthy individuals (n = 140) [OR (95% CI) = 2.62 (1.36-5.09), P(c)= 0.009]. The frequencies of -607A/A, C/A, C/C genotypes were 27.86%, 48.57% and 23.57% in chronic HBV patients and 12.80%, 59.30% and 27.90% in healthy controls, respectively. No significant association at the position -137 was found between the two groups. The frequencies of -607A/-137G haplotype homozygosity were higher in the chronic HBV patients (17.14%) than in the controls (8.57%) [OR (95% CI) = 2.21 (1-4.93), P = 0.05], although this was not statistically significant when corrected for multiple comparison (P(c)= 0.40). In conclusion, this study proposes that A/A genotype at position -607 in IL-18 gene can be used as a new genetic maker in Thai population for predicting chronic hepatitis B development.     

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.     

A matched case-control study of hepatitis B virus mutations in the preS and core promoter regions associated independently with hepatocellular carcinoma

This study aimed to determine hepatitis B virus (HBV) mutations associated independently with the risk of hepatocellular carcinoma (HCC), as adjusted with other mutations in the preS and core promoter regions of HBV genotypes B and C. One hundred and forty HBV-infected patients with HCC and 280 HBV-infected patients without HCC who had intact data of HBV genotyping and DNA sequencing in both regions were involved in this age-, sex-matched case-control study. Univariate and two-step stepwise multivariate regression analyses were performed to determine factors associated with the risk of HCC. Of 39 mutations evaluated, 23 in genotype C and 6 in genotype B were associated with an increased risk of HCC in the univariate analysis. Multivariate analyses established that genotype C (adjusted odds ratio [AOR] = 3.3; 95% confidence interval [CI] = 1.1-9.8), viral load (≥10(4) copies/ml) (AOR = 2.4; 95% CI = 1.0-5.8), A2962G (AOR = 18.7; 95% CI = 7.5-46.7), preS2 start codon mutation (AOR = 12.5; 95% CI = 3.4-45.5), C105T (AOR = 0.1; 95% CI = 0.0-0.2), T1753V (AOR = 3.1; 95% CI = 1.1-9.2), and A1762T/G1764A (AOR = 2.9; 95% CI = 1.1-7.3) were associated independently with HCC, adjusted for factors including mutations in both regions. By using an estimating haplotype frequencies program, it was found that a haplotypic carriage with 105C and 2962G was significantly more frequent in the patients with HCC than in those without HCC and the frequency of haplotype 2962G-preS2 start codon wildtype-105C-1762T/1764A was 47.9% in the patients with HCC and 4.3% in those without HCC. Conclusively, A2962G and T105C are novel factors associated independently with HCC. Further prospective studies are needed to confirm the role of these mutations in the development of HCC.     

Interleukin-10 promoter polymorphisms in patients with systemic lupus erythematosus from the Canary Islands

The purpose of this study was to examine whether several allelic variants in the polymorphic interleukin (IL)-10 promoter region were related with an increased risk of developing systemic lupus erythematosus (SLE) in Spanish patients from Canary Islands. Microsatellites (MS) at positions -4000 and -1200 (IL10R and IL10G, respectively) and single nucleotide polymorphisms (SNPs) (MS) at positions -1082G/A, -819C/T and -592C/A of the IL-10 promoter were analysed in patients with SLE and healthy controls from Canary Islands (Spain). We found that SNPs but not MS were associated with SLE. The GCC haplotype frequency was significantly higher in SLE patients (0.43) than in healthy donors (0.33) [P = 0.02; OR = 1.50 (95% CI = 1.06-2.14)], whereas the ACC haplotype was less represented in patients (0.28 vs. 0.37) [P = 0.02; OR = 0.64 (95% CI = 0.44-0.92)]. To assess the functional role of genotypes, serum IL-10 levels from patients and controls were quantified by ELISA. Also, the lipopolysaccharide-induced IL-10 secretion by monocytes from healthy controls was evaluated in vitro. Serum IL-10 levels were higher in patients [median (interquartile range) = 2.8 pg/mL (1.8-4.2)] than in controls [0.9 pg/mL (0-3.5)] (P = 0.02), but no association was observed between serum IL-10 levels or lipopolysaccharide-induced IL-10 secretion and the IL-10 promoter haplotypes. These data suggest that the IL-10 promoter haplotype that produces higher levels of cytokine is associated with SLE in patients from Canary Islands.     

The polymorphisms of interleukin-10 gene influence the prognosis of patients with advanced melanoma

The interleukin-10 gene (IL-10) is polymorphic. The genotypes result in inter-individual differences in IL-10 production, which may play a role in the pathophysiology and the clinical course of melanoma and other cancers. We analyzed the frequency of the ATA haplotype formed by the alleles at -1082 (G/A), -819 (C/T), and -592 (C/A) at the promoter region of the IL-10 gene in patients with melanoma (n = 108) and healthy subjects (n = 393). We also studied the long-term prognostic significance of the ATA haplotype carriage. There were significantly more ATA carriers in melanoma patients compared with control subjects (44 vs. 33%, respectively, P = 0.03). In the patients who presented with localized disease, the haplotype carriage was not significantly associated with recurrence rate, disease-free survival, or overall survival. In the patients who presented with or developed advanced disease (n = 36), the ATA haplotype carriage [HR 0.47, 95% confidence interval (CI) 0.22-1.01, P = 0.05] was found statistically significant when adjusted by metastatic sites (HR 4.63, 95% CI 1.88-11.44, P = 0.0009) in multivariate analysis for survival. ATA haplotype carriage appears to increase the susceptibility to melanoma. This is not a significant prognostic factor in localized melanoma, but in advanced disease, it implies longer survival.     

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.     

Investigation on the association between inerleukin-10 -592C/A, 819C/T and -1082A/G gene polymorphisms and development of diabetic nephrophathy

We conducted a case-control study to investigate the association between interleukin (IL)-10-592C/A, -819C/T and -1082A/G polymorphisms and susceptibility to diabetic nephropathy. A hospital-based case-control study was taken in our study. A total of 172 patients with proven type 2 diabetes mellitus and 344 controls were recruited from the First Affiliated Hospital of Xinxiang Medical University between March 2012 and October 2014. Genotyping of IL-10 -592C/A, -819C/T and -1082A/G polymorphisms was done by done by PCR-RFLP methods. By the χ² test, the distributions of the GG, GA and AA genotypes in IL-10 -1082A/G were significantly different between patients with diabetic nephropathy and control subjects (χ² = 8.09, P = 0.02). By conditional logistic regression analysis, we found that the AA genotype of IL-10 -1082A/G was associated with an elevated risk of diabetic nephropathy compared to the GG genotype in codominant model, and the adjusted OR (95% CI) was 2.38 (1.23-4.57). In dominant model, the GA+AA genotype was associated with a significantly increased risk of diabetic nephropathy compared to the GG genotype in dominant model (OR = 1.47, 95% CI = 1.05-2.16). In recessive model, the AA genotype could influence the susceptibility to diabetic nephropathy when compared with the GG+GA in recessive model (OR = 2.08, 95% CI = 1.12-3.85). In conclusion, we suggested that IL-10 -1082A/G gene polymorphism was correlated with development of diabetic nephropathy, but no association was observed between IL-10 -819T/C and -592A/C and risk of diabetic nephropathy.     

Association between the Interleukin 10-1082G>A polymorphism and coronary heart disease risk in a Caucasian population: a meta-analysis

Interleukin-10 (IL-10) is a cytokine with anti-inflammatory and B-cell-stimulating activity. IL-10 is expressed in human atherosclerotic plaques and studies have shown the involvement of IL-10 in the atherosclerotic process. The IL-10-1082G/A polymorphism is one of the most commonly studied polymorphisms in this gene because of its association with coronary heart disease (CHD) risks, but previous results have been conflicting. We performed a meta-analysis using six eligible case-control studies (including 14 data sets) with a total of 5006 patients and 3968 controls to summarize the existing data on the association between the IL-10-1082G/A polymorphism and CHD risk. Compared with the common IL-10-1082G/A GG genotype, the carriers of variant genotypes (IL-10-1082GA/AA) had a 1.12-fold elevated risk of CHD (95% CI = 1.01-1.23, P = 0.03) under the dominant genetic model, as estimated using a random effect model. The effect of the IL-10-1082G/A polymorphism was further evaluated using stratification analysis. In the three disease of artery studies, with the variant genotypes had a not obvious increased risk of disease of artery (OR = 1.19, 95% CI = 0.98-1.44, P = 0.08) as estimated using a fixed effect model. Similar results were found in the nine myocardial infarction studies (OR = 1.13, 95% CI = 1.00-1.27, P = 0.05). It was also demonstrated that the increased risk of CHD associated with IL-10-1082G/A variant genotypes was more pronounced in Caucasians (OR = 1.12, 95% CI = 1.01-1.23, P = 0.03). Our meta-analysis suggests that the IL-10-1082G/A polymorphism genotypes (GA+AA) might be associated with an increased risk of CHD, especially in Caucasians.     

The relationship between tumour necrosis factor-α gene polymorphism and susceptibility and clearance of the persistent hepatitis B virus infection in a Chinese population: a meta-analysis

To date, many studies conducted in the Chinese population have determined the correlation between the tumour necrosis factor-α (TNF-α)-238G/A, -308G/A, -857C/T and -863C/A polymorphisms and persistent hepatitis B virus (HBV) infection. However, their results remain inconclusive. With the aim of confirming this correlation, we performed a meta-analysis of 19 studies. The dichotomous data are presented as the OR with a 95% CI. The results of our study indicate that carriers of the TNF-a-857T allele among the pooled Chinese population were more likely to show spontaneous clearance of HBV (T vs C: OR = 0.824, 95% CI = 0.713–0.953, p 0.009; TT vs CC: OR = 0.701, 95% CI = 0.507–0.970, p 0.032; TC vs CC: OR = 0.804, 95% CI = 0.683–0.947, p 0.009; TT + TC vs CC: OR = 0.835, 95% CI = 0.716–0.974, p 0.021). The TNF-a-308A allele was associated with significantly reduced persistent HBV infection risk in the Chinese (A vs G: OR = 0.585, 95% CI = 0.456–0.751, p 0.002; AG vs GG: OR = 0.519, 95% CI = 0.341–0.789, p <0.000; AA + AG vs GG: OR = 0.512, 95% CI = 0.339–0.772, p 0.001). Persistent HBV infection susceptibility is associated with the TNF-α-308G/A gene polymorphism in the Chinese population, whereas HBV clearance is associated with the TNF-α-857C/T gene polymorphism.     

Proximal interleukin-10 gene polymorphisms in Italian patients with systemic sclerosis

Interleukin-10 (IL-10) can favour the development of fibrosis by promoting a relative shift towards T helper 2 responses. Three single base pair substitutions in the 5' flanking region of the IL-10 gene (G/A -1082, C/T -819 and C/A -592) influence the amount of IL-10 secreted in cell cultures: the GCC haplotype is associated with an increased production, while the ACC and the ATA haplotypes are associated with intermediate and decreased production. Accordingly, three phenotypes have been individuated: high producers (GCC+/GCC+), medium producers (GCC+/GCC-) and low producers (GCC-/GCC-). We hypothesised that IL-10 haplotypes and genotypes are differently expressed in patients with systemic sclerosis (SSc) with the limited cutaneous SSc (lcSSc) subset or the diffuse cutaneous SSc (dcSSc) subset. One hundred and sixty-one unrelated Italian patients with SSc and 94 controls have been included. Their DNA was extracted and stored before being analysed by polymerase chain reaction with sequence-specific primers. The GCC haplotype is overrepresented in patients with SSc; subjects with dcSSc were the primary contributors to these results (dcSSc: 52.2% vs controls: 37.2%; chi2= 8.519, 2 d.f., corrected P= 0.04). In Scl70-positive patients, the GCC haplotype increased the likelihood of presenting the dcSSc subset [chi2= 12.56, P < 0.0005; odds ratio (OR) = 3.89, 95% confidence interval (CI(95)) = 1.69-9.08]; these results were confirmed at the phenotypic level (chi2= 11.67, 2 d.f., P= 0.003). In Scl70-positive patients, the high-producing phenotype was associated with poor survival, independently from disease subset and gender (hazard ratio = 9.9, CI(95)= 1.6-61.27, P < 0.05). The IL-10 haplotype and genotype associated with high IL-10 production may alter the susceptibility to SSc and/or its expression, increasing the prognostic value of other well-known markers of disease severity.