• Interleukin-2 (IL-2)
• Multiple myeloma
• Polymorphism
• Prognosis
• Survival

• Humans
• Interleukin-2/genetics
• Multiple Myeloma/drug therapy
• Multiple Myeloma/genetics
• Polymorphism, Single Nucleotide/genetics
• Genotype
• Cytokines/genetics
• Genetic Predisposition to Disease

• disease progression
• genetic polymorphisms
• immune-related genes
• lymphoma
• survival

• Humans
• Genotype
• Lymphoma/genetics
• Polymorphism, Single Nucleotide
• Prognosis
• Proportional Hazards Models
• Genetic Predisposition to Disease
• Case-Control Studies

• National Natural Science Foundation of China

• ARV associated hepatotoxicity
• Cytokine
• Genetic polymorphism
• HIV patients
• IL-2 gene
• NNRTI regimen.

• Bcl-2 family
• DMDD
• MAPK signaling pathway
• breast cancer

• Autoimmune hepatitis
• Cytokine
• Interferon-gamma
• Interleukin-2
• Single nucleotide polymorphism

This study aimed to examine the joint effects of folate intake, polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTRR) and methionine synthase (MTR) genes and breast cancer risk. A case-control study of 570 consecutively recruited breast cancer cases and 576 controls was conducted in Guangzhou, China. Multifactor dimensionality reduction and logistic regression approach were used to evaluate gene-gene interaction. The covariates were chosen based on comparison of baseline characteristics of cases and controls. Folate intake was found to be inversely associated with breast cancer risk. The MTRRrs162036 GG genotype was associated with a decreased risk of breast cancer [adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) 0.20–0.85]. Compared with the wild-type group (MTRRrs162036 AA with MTRrs1805087 AA) MTRRrs162036 AA with MTRrs1805087 GA + GG was associated with a decreased risk (OR 0.70, 95% CI 0.48–1.03). With the combined MTHFRrs1801131 TT and MTHFRrs1801133 GG genotypes as a reference, MTHFRrs1801131 TT with MTHFRrs1801133 GA + AA was associated with a decreased risk (OR 0.78, 95% CI 0.57 – 1.08) and MTHFRrs1801131 GT + GG with MTHFRrs1801133 GA + AA was associated with an increased risk (OR 1.35, 95% CI 0.88–2.05). The joint impact of MTRRrs162036 and MTRrs1805087, MTHFRrs1801131 and MTHFRrs1801133, folate and MTHFRrs1801133 may contribute to breast cancer risk.

Several epidemiological studies have illustrated that polymorphisms in interleukin-2 (IL-2) were associated with diverse cancer types. However, recently published statistics were inconsistent and inconclusive. Therefore, the current meta-analysis was performed to elaborate the effects of IL-2 polymorphisms (rs2069762 and rs2069763) on cancer susceptibility.

A total of 5,601 cancer cases and 7,809 controls from 21 published case–control studies were enrolled in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between IL-2 polymorphisms and cancer susceptibility.

Our study demonstrated an increased susceptibility to cancer in rs2069762 (G vs T: OR =1.268, 95% CI =1.113–1.445; GG vs TT: OR =1.801, 95% CI =1.289–2.516; GT vs TT: OR =1.250, 95% CI =1.061–1.473; GG + GT vs TT: OR =1.329, 95% CI =1.118–1.579; GG vs GT + TT: OR =1.536, 95% CI =1.162–2.030). In the subgroup analysis, increased susceptibility to cancer was identified in the hospital-based group and P_HWE<0.05 (P-value of the Hardy–Weinberg equilibrium [HWE]) group. In addition, a positive association with cancer susceptibility was observed among both Chinese and non-Chinese. However, no relationship was detected between the rs2069763 polymorphism of IL-2 and cancer susceptibility.

To conclude, rs2069762 polymorphism of IL-2 contributed to an increased susceptibility to cancer, whereas no association was identified between rs2069763 polymorphism and cancer susceptibility. Further detailed studies are warranted to confirm our findings.

• IL-2
• cancer
• meta-analysis
• polymorphism

The search for biomarkers that characterize specific aspects of inflammatory bowel disease (IBD), has received substantial interest in the past years and is moving forward rapidly with the help of modern technologies. Nevertheless, there is a direct demand to identify adequate biomarkers for predicting and evaluating therapeutic response to different therapies. In this subset, pharmacogenetics deserves more attention as part of the endeavor to provide personalized medicine. The ultimate goal in this area is the adjustment of medication for a patient’s specific genetic background and thereby to improve drug efficacy and safety rates. The aim of the following review is to utilize the latest knowledge on immunopathogenesis of IBD and update the findings on the field of Immunology and Genetics, to evaluate the response to the different therapies. In the present article, more than 400 publications were reviewed but finally 287 included based on design, reproducibility (or expectancy to be reproducible and translationable into humans) or already measured in humans. A few tests have shown clinical applicability. Other, i.e., genetic associations for the different therapies in IBD have not yet shown consistent or robust results. In the close future it is anticipated that this, cellular and genetic material, as well as the determination of biomarkers will be implemented in an integrated molecular diagnostic and prognostic approach to manage IBD patients.

• Mucosal immunology
• Biomarkers
• Pharmacology
• Mode of action
• Therapeutic drug monitoring

• Animals
• Anti-Inflammatory Agents/adverse effects
• Anti-Inflammatory Agents/pharmacokinetics
• Anti-Inflammatory Agents/therapeutic use
• Biotransformation/genetics
• Diagnostic Imaging/methods
• Drug Monitoring/methods
• Gastrointestinal Agents/adverse effects
• Gastrointestinal Agents/pharmacokinetics
• Gastrointestinal Agents/therapeutic use
• Genetic Markers
• Genetic Predisposition to Disease
• Humans
• Inflammation Mediators/immunology
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/immunology
• Molecular Diagnostic Techniques
• Phenotype
• Predictive Value of Tests
• Treatment Outcome

Some studies have investigated the association of IL-2 -330T/G (rs2069762) polymorphism with cancer risk, but the previous results were conflicting and had relatively low statistical power. Thus, we performed a meta-analysis to derive a more precise estimation of the association between IL-2 -330T/G polymorphism and cancer risk.

A literature search was performed systematically using electronic databases. The odds ratio (OR) with 95% confidence interval (CI) was used to estimate the pooled effect.

A total of ten studies including 3,060 cases and 3,435 controls were involved in this meta-analysis. The results indicated that IL-2 -330T/G polymorphism was significantly associated with cancer risk ([OR =2.03, 95% CI =1.40–2.95] for GG vs TT; [OR =1.37, 95% CI =1.11–1.69] for GT vs TT; [OR =1.46, 95% CI =1.18–1.81] for [GG + GT] vs TT; [OR =1.66, 95% CI =1.24–2.23] for GG vs [GT + TT]; and [OR =1.35, 95% CI =1.16–1.57] for G vs T). In the subgroup analysis according to cancer type, significant association was found in lymphoma ([OR =1.46, 95% CI =1.11–1.91] for GT vs TT; [OR =1.58, 95% CI =1.22–2.05] for [GG + GT] vs TT; [OR =1.84, 95% CI =1.22–2.77] for GG vs [GT + TT]) and other cancers, but not in gastric cancer. In the subgroup analysis by ethnicity, the significant risk was found among Asians, but not among Europeans.

This meta-analysis suggests that IL-2 -330T/G polymorphism has an increased risk of cancer in Asians. However, further detailed studies are still required to confirm our findings.

• IL-2
• cancer
• meta-analysis
• polymorphism
• risk

• Chronic hepatitis B
• Hepatocellular carcinoma
• Interleukin-2
• Liver cirrhosis
• Polymorphism

Ca²⁺/nuclear factor of activated T-cells (Ca²⁺/NFAT) signaling pathway may play a crucial role in Kawasaki disease (KD). We investigated 16 genetic variants, selected by bioinformatics analyses or previous studies, in 7 key genes involved in this pathway in a Chinese population. We observed a significantly or marginally increased KD risk associated with rs2720378 GC + CC genotypes (OR = 1.39, 95% CI = 1.07–1.80, P = 0.014) or rs2069762 AC + CC genotypes (OR = 1.28, 95% CI = 0.98–1.67, P = 0.066), compared with their wild type counterparts. In classification and regression tree analysis, individuals carrying the combined genotypes of rs2720378 GC or CC genotype, rs2069762 CA or CC genotype and rs1561876 AA genotype exhibited the highest KD risk (OR = 2.12, 95% CI = 1.46–3.07, P < 0.001), compared with the lowest risk carriers of rs2720378 GG genotype. Moreover, a significant dose effect was observed among these three variants (P_trend < 0.001). In conclusion, this study implicates that single- and multiple-risk genetic variants in this pathway might contribute to KD susceptibility. Further studies on more comprehensive single nucleotide polymorphisms, different ethnicities and larger sample sizes are warranted, and the exact biological mechanisms need to be further clarified.

Although case–control studies have evaluated the role of variant inflammatory-related loci in prostate cancer, their impact is virtually unknown among men of African descent. To address this, we evaluated the impact of inflammatory cytokine single nucleotide polymorphisms (SNPs) on prostate cancer risk for men of African descent.

Forty-four SNPs in inflammatory cytokine-associated genes were evaluated among 814 African-American and Jamaican men (279 prostate cancer cases and 535 controls) using Illumina’s Golden gate genotyping system. Individual SNP effects were evaluated using logistic regression analysis.

Four SNPs were modestly associated with prostate cancer after adjusting for age. In the total population, inheritance of the IL1R2 rs11886877 AA, IL8RB rs11574752 AA, TNF rs1800629 GA + AA, and TNF rs673 GA genotypes modestly increased prostate cancer risk by 1.45 to 11.7-fold relative to the referent genotype. Among U.S. men, age-adjusted dominant, recessive and additive genetic models for the IL1R2 rs11886877 locus were linked to an increase in prostate cancer susceptibility. However, these main effects did not persist after adjusting for multiple hypothesis testing.

Our preliminary data does not strongly support the hypothesis that inflammatory-related sequence variants influence prostate cancer risk among men of African descent. However, further evaluation is needed to assess whether other variant inflammatory-related genes may contribute to prostate cancer risk and disease progression in larger and ethnically diverse multi-center studies.

The selection pressure imposed by the parasite has a functional consequence on the immune genes, leading to altered immune function in which regulatory T cells (Tregs) induced by parasites during infectious challenges modulate or thwart T effector cell mechanism.

We identified and investigated regulatory polymorphisms in the immune gene IL2 and its receptor IL2R alpha (also known as CD25) in Gabonese individuals exposed to plentiful parasitic infections.

We identified two reported variants each for IL2 and its receptor IL2R alpha gene loci. Also identified were two novel variants, -83 /-84 CT deletions (ss410961576) for IL2 and -409C/T (ss410961577) for IL2R alpha. We further validated all identified promoter variants for their allelic gene expression using transient transfection assays. Three promoter variants of the IL2 locus revealed no significant expression of the reporter gene. The identified novel variant (ss410961577C/T) of the IL2R alpha revealed a significant higher expression of the reporter gene in comparison to the major allele (P<0.05). In addition, the rs12722616C/T variant of the IL2R alpha locus altered the transcription factor binding site TBP (TATA box binding protein) and C/EBP beta (CCAAT/enhancer binding protein beta) that are believed to regulate the Treg function.

The identification and validation of such regulatory polymorphisms in the immune genes may provide a basis for future studies on parasite susceptibility in a population where T cell functions are compromised.