Li-Juan Qiu

Lung, liver, prostate, bladder malignancies risk in systemic lupus erythematosus: evidence from a meta-analysis

Objective: The objective of this paper is to examine some solid tumors incidence in patients with systemic lupus erythematosus (SLE) derived from population-based cohort studies by means of meta-analysis. Methods: Relevant electronic databases were searched for studies characterizing the associated risk of overall malignancy and four site-specific malignancies (lung, liver, prostate, bladder cancer) in patients with SLE. The meta-analysis procedure was used to pool standardized incidence rates (SIRs) with 95% confidence intervals (CIs) to evaluate the association. Results: A total of seven cohort studies were identified, of which six provided the SIR for overall malignancy, seven reported the SIR for lung cancer, five for liver cancer, four for prostate cancer and six for bladder cancer. Overall, lung and liver cancers were more frequently observed in patients with SLE with SIR of 1.16 (95% CI = 1.12–1.21), 1.68 (95% CI = 1.33–2.13) and 2.44 (95% CI = 1.46–4.05), respectively. However, the risk of prostate cancer appeared to be somewhat reduced in male patients with SLE (SIR = 0.71, 95% CI = 0.57–0.89). Conclusions: This meta-analysis shows that SLE patients are at increased risk of developing cancer, particularly of the lung, bladder and liver. However, males with SLE have a decreased risk of prostate cancer.

Meta-analysis of association between cytokine gene polymorphisms and Behcet's disease risk

The aim of this study was to perform a meta‐analysis of eligible studies to derive precise estimation of the association of interleukin‐1 (IL‐1), IL‐10 and tumor necrosis factor (TNF)‐α polymorphisms with Behcets disease (BD). Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 4003 cases and 4748 controls in 19 eligible studies were included in the meta‐analysis. We examined the relationship between seven single nucleotide polymorphisms (SNPs) in the above‐mentioned three cytokine genes and susceptibility to BD. Meta‐analysis indicated the association between the cytokine gene polymorphisms in all study subjects in the allelic model (TNF‐α ‐308A/G: OR = 0.73, 95% CI: 0.61–0.88, P = 0.001; IL‐10 ‐819C/T: OR = 0.72, 95% CI: 0.66–0.78, P < 0.001; IL‐10 ‐592C/A: OR = 0.74, 95% CI: 0.64–0.86, P < 0.001); the dominant model (TNF‐α ‐308A/G: OR = 0.77, 95% CI: 0.64–0.92, P = 0.004; IL‐10 ‐1082G/A: OR = 1.64, 95% CI: 1.10–2.44, P = 0.014); the recessive model (TNF‐α ‐308A/G: OR = 0.27, 95% CI: 0.12–0.65, P = 0.003; IL‐10 ‐819C/T: OR = 0.71, 95% CI: 0.57–0.90, P = 0.004). However, no significant evidence for the associations of IL‐1α ‐889C/T, IL‐1β ‐551C/T, IL‐1β ‐3962C/T polymorphisms with BD susceptibility was detected. The present study might suggest that TNF‐α ‐308A/G, IL‐10 ‐1082G/A, ‐819C/T, ‐592C/A polymorphisms are associated with BD susceptibility.

Relationship between the IL-4 gene promoter -590C/T (rs2243250) polymorphism and susceptibility to autoimmune diseases: a meta-analysis

Studies investigating the association between interleukin (IL)‐4 gene promoter ‐590C/T (rs2243250) polymorphism and autoimmune diseases report conflicting results. To derive a more precise estimation of the relationship, a meta‐analysis was performed.

CTLA-4 CT60 (rs3087243) polymorphism and autoimmune thyroid diseases susceptibility: a comprehensive meta-analysis

Abstract Objective: To determine whether the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) CT60 polymorphism (rs3087243) confers susceptibility to autoimmune thyroid disease (AITDs). Methods: A meta-analysis was performed using: (1) allelic contrast, (2) recessive model and (3) dominant model. Electronic search of PubMed, Medline and Chinese National Knowledge Infrastructure (CNKI) was conducted to select studies. Results: Finally, a total of 20 separate studies were available for the current meta-analysis: Graves’ disease (GD): 18 studies including 1 Iranian, 6 Caucasian and 11 Asian populations; Hashimoto’s thyroiditis (HT): seven studies including one Iranian, three Caucasian and three Asian populations. A significant association was found between the CTLA-4 CT60 polymorphism (rs3087243) and GD, with regard to comparisons between allele and genotype frequencies (all p < 0.001). After stratification by ethnicity, significant relationships were consistently identified both in Caucasian and Asian populations. Furthermore, the association between this allelic variant and HT risk was also found in overall and Asian populations (OR: 1.26, 95% CI: 1.10–1.44; OR: 1.45, 95% CI: 1.19–1.76, respectively). Conclusion: Taken together, our study suggested that the CT60 polymorphism (rs3087243) in CTLA-4 gene might confer susceptibility to the AITDs (GD/HT).

Association of signaling transducers and activators of transcription 1 and systemic lupus erythematosus

Abstract Systemic lupus erythematosus (SLE) is complex autoimmune disease which involves various facets of the immune system. Signaling transducers and activators of transcription 1 (STAT1) belongs to the family of STAT transcription factors that mediate various biological responses. Recently, studies in both experimental animal models of lupus and patients with SLE have revealed expression and activation of STAT1 is closely associated with the pathogenesis of SLE. Moreover, increased production of interferons (IFNs) and aberrant activation of IFNs signaling, which is mechanistically linked to increased level of STAT1, are crucial for the development of SLE. Therefore, we will focus on the association of STAT1 and SLE based on recent understandings to render more information about the mechanisms of STAT1 might perform in. Hopefully, the information obtained will lead to a better understanding of the development and pathogenesis of systemic autoimmune diseases, as well as its clinical implications and therapeutic potential.

Association of CTLA-4 variants with susceptibility to inflammatory bowel disease: A meta-analysis

OBJECTIVE The aim of this study was to determine whether CTLA-4 gene variants were associated with susceptibility to inflammatory bowel disease (IBD). METHODS Meta-analysis was conducted on the association between CTLA-4 variants and IBD using: (1) allelic contrast, (2) the recessive model, and (3) the dominant model. RESULTS A total of 9 relevant studies including 1739 Crohns disease (CD) cases, 10 relevant studies containing 1017 ulcerative colitis (UC) cases and 2685 healthy controls were involved in this meta-analysis. Overall, CTLA-4+49A/G, -318C/T and CT60 variants were not associated with IBD susceptibility in all genetic models (P>0.05). Stratification by ethnicity indicated a significant association between the CTLA-4+49A/G variant and CD in Caucasian group (GG vs. GA+AA: OR=0.723, 95% CI=0.564-0.926, P=0.010). In Asian group, meta-analysis showed a significant association between the CTLA-4 CT60 variant and UC (AA vs. AG+GG: OR=0.375, 95% CI=0.163-0.861, P=0.021). CONCLUSIONS Based on the published literature, this meta-analysis suggests that the CTLA-4+49A/G variant may be related to CD susceptibility in Caucasians, and the CTLA-4 CT60 variant may be associated with UC susceptibility in Asians.

Interleukin-7 Receptor Single Nucleotide Polymorphism rs6897932 (C/T) and the Susceptibility to Systemic Lupus Erythematosus

Emerging evidences were accumulated to support the view that aberrant interleukin-7 (IL-7) signaling might be associated with autoimmunity. Former studies demonstrated the single nucleotide polymorphism (SNP) rs6897932 C/T in the IL-7 receptor (IL-7R) gene was associated with susceptibility to autoimmune diseases, including multiple sclerosis and type I diabetes. Given these, this study was conducted to investigate whether an association existed between SNP rs6897932 and the susceptibility to systemic lupus erythematosus (SLE), a severe systemic autoimmune disease. In this context, 816 SLE patients and 816 controls from a Chinese population were recruited for this study, and the results showed that the major allele C of rs6897932 showed a higher frequency in SLE patients compared with controls (P = 0.039, C versus T); significant difference was also detected under a recessive model with regard to the distribution of genotype frequencies between SLE patients and controls (P = 0.041, CC versus CT + TT), which was not consistent with the results under a dominant model (P = 0.349, CC + CT versus TT). Moreover, association studies were also performed contraposing the relationship between the SNP rs6897932 C/T and lupus nephritis as well as 10 clinical features of SLE; however, no significant association signal was found regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of 11 sub-phenotypes. In conclusion, the major allele C of SNP rs6897932 may be associated with increased SLE risk in Chinese populations, and further studies are still encouraged to shed light on the true associations between SLE and its susceptibility genes with respect to IL-7R gene.

Associations of Interleukin-4 Receptor Gene Polymorphisms (Q551R, I50V) with Rheumatoid Arthritis: Evidence from a Meta-Analysis

BACKGROUND AND AIMS Published data on the associations between interleukin-4 receptor (IL-4R) gene polymorphisms (Q551R, I50V) and rheumatoid arthritis (RA) risk are controversial. To quantitatively evaluate the relationships, a meta-analysis was performed. METHODS Studies were identified from the databases of PubMed, MEDLINE, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure, with the last report up to June 2012. The effect summary odds ratio (OR) and 95% confidence interval (CI) were obtained. RESULTS A total of six separate comparisons involving 2173 patients and 1892 controls were included to assess the association of IL-4R gene Q551R polymorphism and RA susceptibility. Overall, no significantly elevated RA risk was found in the meta-analysis. The pooled OR for the minor R allele was 0.942 (95% CI: 0.848-1.047, p=0.268) in patients with RA. After stratification by ethnicity, there was still no significant association detected in the European population (OR=0.979, 95% CI: 0.875-1.094). As for I50V polymorphism, there were four comparisons involving 1653 patients and 1584 controls in this meta-analysis. The pooled OR for the V allele was 1.104 (95% CI: 1.001-1.217) in RA, the V allele of the IL-4R gene I50V variant might be a risk factor for RA. However, the relationship between the V allele of IL-4R gene I50V polymorphism and rheumatoid factor positive in patients with RA was not identified through a minor meta-analysis, including four independent relevant comparisons. CONCLUSIONS This meta-analysis indicates that the I50V polymorphism of IL-4R gene may confer susceptibility to RA; up to now, there is still not enough evidence to reveal the association of the IL-4R gene Q551R polymorphism with RA risk.