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

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

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.     

IL-10 promoter nt -1082A/G polymorphism and human papillomavirus infection in cytologic abnormalities of the uterine cervix.

The role of A/G polymorphism at nucleotide -1082 in the interleukin-10 (IL-10) promoter was assessed by following the disease course of 253 patients who had had a routine diagnostic Hybrid Capture human papillomavirus (HPV) test because of cytologic or colposcopic abnormalities of the uterine cervix. At baseline, 97 (78%) of the 125 high-risk HPV-positive and 83 (65%) of the 128 HPV-negative patients had equivocal cytologic atypia classified as P3 by the Papanicolaou classification, and the rest of the patients had mild colposcopic atypia with cytologic results of no oncogenic significance. In the high-risk HPV-infected patients, the frequency distribution of the nt -1082 genotypes (A/A: 28%; A/G: 52%; G/G: 20%) did not differ significantly from that in the controls (A/A: 25%; A/G: 51%; G/G: 24%; p = 0.70). On the other hand, the nt -1082 G allele tended to decrease susceptibility to equivocal cytologic atypia unrelated to HPV infection (A/G: OR = 0.56 [95% CI: 0.31-1.02], G/G: OR = 0.27 [95% CI: 0.11-0.63], p for trend = 0.05). With respect to the development of high-grade cervical intraepithelial neoplasia (CIN), the established risk factors, such as high-risk HPV infection (RR = 104.6, 95% CI: 14.2-769.9) and cytologic atypia (RR = 9.6, 95% CI: 2.34-39.7) but not the various nt -1082 genotypes (A/A: reference; A/G: RR = 1.11 [95% CI: 0.59-2.08]; G/G: RR = 0.62 [95% CI: 0.25-1.50]) were found to increase the risk for high-grade CIN. In conclusion, the nt -1082 polymorphism had no influence on the early phase of cervical carcinogenesis but may determine different susceptibilities to cervical abnormalities unrelated to HPV infection.     

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

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

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.     

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

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

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

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

CYP1A1-HincⅡ和GSTT1基因遗传多态性与原发性痛经关系分析

目的 研究原发性痛经的遗传易感性。方法 收集某纺织厂499名新婚女工的资料,采用Logistic回归分析,评价CYP1A1－Hinc II和GSTT1多态性与重度原发性痛经的关系。结果 在未调整环境因素时CYP1A1－Ainc II变异基因型虽对痛经有缓解趋势。但差异无显著性（CYP1A1－Hinc II:OR=0.64 95%CI：0．35－1．17）,而GSTT1变异基因型可增加重度原发性痛经危险性（GSTT1：OR＝1。83,95％,CI：1．04－3．21）。调整潜在环境影响因素后,CY1A1－Hinc II变异基因型显示对原发性痛经有缓解趋势（CYP1A1－Hinc II,OR=0.58,95%,CI:0.31-1.08),但差异仍无显著性,而GSTT1变异基因型仍显示可增加重度原发性痛经的危险性（GSTT1：OR＝2．01,95％,CI：1．12－3．62）。结论 重度原发性痛经与GSTT1遗传多态性相关。     

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.     

Associations between interleukin-10 polymorphisms and susceptibility to psoriasis: a meta-analysis

Objective

The aim of this study was to determine whether three specific interleukin-10 (IL-10) polymorphisms confer susceptibility to psoriasis.

Methods

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

Results

A total of eight studies involving 1,018 psoriasis patients and 1,186 controls were considered in the meta-analysis. No association was found between psoriasis and the IL-10-1082 G allele in all study subjects [odds ratio (OR)?=?1.098, 95?% confidence interval (CI)?=?0.923?1.306, p?=?0.291] or between this allele and psoriasis in Europeans (OR?=?0.990, 95?% CI?=?0.809?1.214, p?=?0.925), but a significant association was found in Asians (OR?=?1.785, 95?% CI?=?1.144?2.76, p?=?0.011). Three polymorphisms at the promoter region of IL-10 (-1082 G/A, -819 C/T, -592 C/A) are known to be in complete linkage disequilibrium, but no association was found between the haplotype and psoriasis.

Conclusions

This meta-analysis shows that the IL-10-1082 G/A polymorphism confers susceptibility to psoriasis in Asians, and suggests that the IL-10 promoter -1082 polymorphism has an ethnicity-specific effect.     

Lack of association between DNA repair gene ERCC1 polymorphism and risk of lung cancer in a Chinese population

The ERCC1 (Excision Repair Cross Complementation Group 1) gene is involved in the nucleotide excision repair pathway. This study was designed to examine whether ERCC1 Asn118Asn (G19007A) polymorphism, which has been associated with risk of some cancers among Caucasians, may be associated with risk of lung cancer in a Chinese population. ERCC1 Asn118Asn (G19007A) genotypes were determined in DNA samples from 151 cases and 143 controls. The distribution of genotypes between cases and controls was not associated with an increased risk of lung cancer (AA versus GG: adjusted OR (odds ratio) = 1.41, 95% CI (confidence interval) = 0.76-2.59; AG versus GG: adjusted OR = 0.78, 95% CI = 0.47-1.29; and AA + AG versus GG: adjusted OR = 0.93, 95% CI = 0.73-1.19). The frequency A (0.20) of the A-allele was significantly lower among these Chinese controls than in the Caucasian control populations (A = 0.54-0.65) (All P < 0.001). No statistically significant effects of age, histological subtype or smoking were found. These findings suggest that ERCC1 Asn118Asn (G19007A) polymorphism may play a limited role for lung cancer in this Chinese population.     

Association between survivin -31G > C promoter polymorphism and cancer risk: a meta-analysis

Survivin is an inhibitor of apoptosis protein and has a crucial role in the development of cancer. The survivin -31G>C (rs9904341) promoter polymorphism influences survivin expression and has been implicated in cancer risk. However, conflicting results have been published from studies on the association between survivin -31G>C polymorphism and the risk of cancer. To clarify the role of this polymorphism in cancer, we performed a meta-analysis of all available and relevant published studies, involving a total of 3485 cancer patients and 3964 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results indicated that the variant genotypes were associated with a significantly increased cancer risk (CC vs GG: OR=1.58, 95% CI=1.20-2.10; CC/GC vs GG: OR=1.23, 95% CI=1.00-1.51; CC vs GG/GC: OR=1.51, 95% CI=1.23-1.85). In the stratified analyses, significantly increased risk was associated with the Asian populations (CC vs GG: OR=1.67, 95% CI=1.16-2.40; CC vs GG/GC: OR=1.50, 95% CI=1.17-1.91). We also performed the analyses by cancer type, and no statistical association was observed. The results suggest that the survivin -31G>C promoter polymorphism might be associated with an increased risk of cancer, especially in the Asian populations.     

Association between angiotensin I-converting enzyme gene polymorphism and susceptibility to cancer: a meta analysis

Background: Angiotensin I-converting enzyme (ACE) gene plays an important role in the pathogenesis of cancers. The association between ACE insertion/deletion (I/D) polymorphism and the risk of various cancers has been studied. However, the results of these studies remain conflicting. Therefore, we performed a meta-analysis to evaluate the association between ACE I/D polymorphism and the risk of cancers. Methods: PubMed, Embase, ScienceDirect, Springer, CNKI, Wanfang, Weipu, CBM databases and Google Scholar were searched for case-control studies on ACE I/D polymorphism and the risk of cancers, published up to Dec 31, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association between ACE I/D polymorphism and cancer risk. Results: Thirty-five published studies with 5007 cases and 8173 controls were included. Overall, there were no significant association between ACE I/D polymorphism and the risk of cancers (II vs. ID+DD OR = 1.05, 95% CI = 0.89-1.23, I vs. D OR = 1.00, 95% CI = 0.89-1.13). However, when stratified by ethnicity, we found a significant association between this polymorphism and cancer risk in Caucasians (II vs. ID+DD: OR = 1.43, 95% CI = 1.02-2.00, I vs. D: OR = 1.23, 95% CI 1.01-1.49). Conclusion: ACE I/D polymorphism is associated with the cancer risk in Caucasians.     

The E-cadherin (CDH1)--160 C/A polymorphism and prostate cancer risk: a meta-analysis

Published data on the association between E-cadherin (CDH1) -160 C/A polymorphism and prostate cancer (PCA) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A logistic regression approach proposed for molecular association studies was used to estimate a biological model of the gene effect. A total of 11 studies including 2637 cases and 2673 controls were involved in this meta-analysis. Logistic regression analysis indicated that the CDH1 -160 C/A genotypes were associated with PCA risk. The genetic model test indicated that the genetic model was most likely to be dominant (CA+AA vs CC). Overall, meta-analysis indicated that the -160A allele carriers (CA+AA) had a 21% elevated risk of PCA, when compared with the homozygotes (CC) (odds ratio (OR)=1.21; 95% confidence interval (CI): 0.97-1.51; P=0.090, P(heterogeneity)=0.001). In the subgroup analyses by ethnicity, significantly elevated risks were associated with -160 variant genotypes (CA+AA) in both European and Asian populations (OR=1.24; 95% CI: 1.08-1.43; P=0.003, P(heterogeneity)=0.220 and OR=1.54; 95% CI: 1.23-1.93; P<0.001, P(heterogeneity)=0.200). However, no significant associations were found in Africans (OR=0.59; 95% CI: 0.32-1.09; P=0.090, P(heterogeneity)=0.070). Although some modest bias could not be eliminated, this meta-analysis suggests that the CDH1 -160A allele is a low-penetrant risk factor for developing PCA, especially in Europeans and Asians.     

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.     

Association and interaction of the TNF-alpha gene with other pro- and anti-inflammatory cytokine genes and HLA genes in patients with type 1 diabetes from North India

Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where major histocompatibility complex (MHC) genes and the insulin-linked polymorphic region have been shown to play major roles. We report here an integrated effect of tumor necrosis factor (TNF) alpha with other cytokine genes. The TNF-alpha-308 GA and AA (high secretor) polymorphisms were significantly increased in the patients with T1D (n = 235) [P < 7 x 10(-6), odds ratio (OR) = 3.04, 95% confidence interval (CI) = 1.8-5.3] compared with the controls (n= 128). The variants of interferon-gamma (IFN-gamma) (A(+874)T), interleukin (IL)-6 (G(-174)C), IL-10 (A(-1082)G, T(-819)C, C(-592)A) and transforming growth factor (TGF) beta1 (T(cdn10)C, G(cdn25)C) did not show a significant difference between patients and controls. However, simultaneous presence of TNF-alpha-308 GA+AA along with both high and low secretor genotypes of IFN-gamma (P < 0.003) was significantly increased in patients. Simultaneous presence of TNF-alpha-308 GA + AA along with high secretor genotypes of IL-6 (P < 0.0001, OR = 2.61, 95% CI = 1.5-4.56), IL-10 (P < 0.0001, OR = 4.26, 95% CI = 1.9-10.1) and TGF-beta1 (P < 0.00004, OR = 2.8, 95% CI = 1.6-4.86) was also significantly increased in patients with T1D. Low secretor genotype of TNF-alpha-308 GG along with low secretor genotypes of IFN-gamma (P < 0.001, OR = 0.465, 95% CI = 0.28-0.77), high secretor genotypes of IL-6 (P < 0.000004, OR = 0.76, 95% CI = 0.227-0.621) and TGF-beta1 (P < 0.000006, OR = 0.336, 95% CI = 0.198-0.568) was protective. The TNF-alpha-308 G allele was in linkage disequilibrium (LD) with the human leukocyte antigen (HLA)-B*0801-DRB1*0301 haplotype, while TNF-alpha-308 A allele was in LD with the HLA-B*5001-DRB1*0301 and B*5801-DRB1*0301 haplotypes, suggesting that the effect of TNF-alpha -308 A allele is not because of its being in LD with any HLA alleles, but because of its functional role and its integrated effect with other cytokines.     

Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility

Aim: Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. Methods: 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. Results: The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). Conclusion: we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.     

IL-1 gene polymorphisms and genetic susceptibility of gallbladder cancer in a north Indian population

Long-standing gallstones are generally present in 65-80% patients of gallbladder cancer (GBC). It has also been suggested that inflammation caused by gallstones may be involved in the development of GBC. Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1 beta (IL-1B) are proinflammatory cytokine genes at the interleukin-1 locus, and polymorphisms of these genes have been associated with various inflammatory diseases. The aim of this study was to investigate whether polymorphism in the IL-1RN and IL-1B genes are associated with GBC patients with and without gallstones. Polymorphisms within the IL-1RN 86-base pair VNTR (variable number tandem repeat) and IL-1B (-511C --> T) were genotyped using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism in 166 healthy subjects and 124 GBC patients. The frequency of the IL-1RN, VNTR 2/2 genotype was significantly higher in GBC patients [P = 0.017; odds ratio (OR) = 3.25; 95% confidence interval (CI) = 1.23-8.58]. CC genotype and 'C' allele of the -511IL-1B C --> T polymorphism also showed high risk for GBC (P = 0.033; OR = 3.36; 95%CI = 1.52-7.43, P = 0.047, OR = 1.41; 95%CI = 1.00-1.98, respectively). The higher cancer risk due to the IL-1RN, 2/2 genotype was observed in GBC patients with or without stones (P = 0.038; OR = 3.58; 95%CI = 1.08-11.65, P = 0.035; OR = 3.33; 95%CI = 1.08-10.61). Risk due to the CC genotype of IL-1B, however, was confined to GBC patients harboring gallstones (P = 0.0003; OR = 6.92; 95%CI = 2.65-18.03). The haplotype 1/C of IL-1RN and IL-1B was found to confer a significantly enhanced risk of GBC in cancer patients with gallstones (P = 0.022; OR = 2.19; 95%CI = 1.12-4.27), while higher risk resulting from 2/C haplotype was of borderline significance (P = 0.061; OR = 3.04; 95%CI = 0.95-9.70). Individuals with 1/C and 2/C haplotypes of IL-1RN VNTR and -511IL-1B C --> T polymorphisms were more susceptible to develop GBC with gallstones compared to healthy controls in north India.     

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.