Yin-Guang Fan

Association of IFIH1 rs1990760 polymorphism with susceptibility to autoimmune diseases: A meta-analysis

Abstract Published data on the association between the IFIH1 rs1990760 polymorphism and multiple autoimmune diseases are controversial and inconclusive. To more precisely estimate the association between the IFIH1 rs1990760 polymorphism and susceptibility to autoimmune diseases, a meta-analysis was conducted. Studies examining the association of the IFIH1 rs1990760 polymorphism with autoimmune diseases were exhaustively searched using PubMed, Web of Science and a review of the references. A total of 19 studies with 26 comparisons including 8 type 1 diabetes (T1D), 5 systemic lupus erythematosus (SLE), 5 Graves’ disease (GD), 2 multiple scleorosis (MS), 2 rheumatoid arthritis (RA), 2 Hashimotos thyroiditis (HT), 2 autoimmune Addison’s disease (AAD) were available for this meta-analysis. Meta-analysis was performed for genotype T/T + T/C (dominant model), genotype T/T (recessive model) and T-allele in fixed or random-effects models. The overall odds ratios (ORs) and 95% confidence intervals (CIs) for T-allele were T1D (OR = 1.184, 95% CI = 1.142–1.229), SLE (OR = 1.143, 95% CI = 1.073–1.217), MS (OR = 1.181, 95% CI = 1.062–1.313) and RA (OR = 1.115, 95% CI = 1.004–1.239), respectively. For T1D and SLE, significant association was observed in the population of European ancestry, but not in the Asian population. This meta-analysis demonstrates that the IFIH1 rs1990760 T-allele confers susceptibility to T1D, SLE, MS and RA and suggests that the IFIH1 rs1990760 polymorphism might have no effect on GD and AAD. Our result provides further evidence for the notion of common gene underlying multiple autoimmune diseases.

The dual nature of Ets-1: focus to the pathogenesis of systemic lupus erythematosus.

E26 transformation-specific-1 (Ets-1) belongs to the Ets family of transcription factors which share a common 85-amino-acid DNA-binding domain. Ets-1 is essential to regulation of the immune system including immune cell proliferation and differentiation. Past data demonstrated Ets-1 play a role in negative regulation of Th17 cells and B cells differentiation. Recently, association of genetic variation in Ets-1 with susceptibility to systemic lupus erythematosus (SLE) have been independently identified by two Genome-wide association studies (GWAS), and decreased Ets-1mRNA level in peripheral blood mononuclear cells (PBMCs) of SLE patients has been reported. All these findings suggest that the transcription factor is broadly linked to the pathogenesis of this disease. However, aberrant control of other immune cells and effector molecules illuminated the complexities of Ets-1 biology. In this review article, we will focus on the dual nature of Ets-1 and discuss its regulatory capability. Hopefully the information obtained will lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for SLE.

Association of the − 1082G/A polymorphism in the interleukin-10 gene with systemic lupus erythematosus: A meta-analysis

A great many studies have investigated the -1082G/A polymorphism (rs1800896) in the interleukin-10 gene (IL10) with SLE susceptibility, but the results are inconsistent and inconclusive. The aim of this meta-analysis was in order to more precisely estimate the relationship. The databases of Pubmed and Web of Science updated to Oct, 2012 were retrieved. Odds ratio (OR) and corresponding 95% confidence interval (95%CI.) as effect size were calculated by fixed-effect model. Analysis for allele contrast of stratification by ethnicity in either Asian or Caucasian, as well as in overall population indicated no significant association (Overall: OR 1.096, 95%CI. 0.995-1.207; Asian: OR 1.204, 95%CI.: 0.944-1.535; Caucasian: OR 1.075, 95%CI.: 0.961-1.202). Analysis for recessive model showed no association in overall populations and in Caucasian (Overall: OR 1.135, 95%CI.: 0.945-1.362; Caucasian: OR 1.069, 95%CI.: 0.882-1.296), but significant association in Asian (OR: 2.848; 95%CI.: 1.194-6.791). Analysis for dominant model indicated that the variant G allele carriers (GG+GA) may have increased the risk of SLE when compared with the homozygote AA in overall populations and in Caucasian (Overall: OR 1.203, 95%CI.: 1.029-1.407; Caucasian: OR 1.233, 95%CI.: 1.014-1.499), but not in Asian (OR: 1.154; 95%CI.: 0.856-1.557). Significant association was found by using homozygote contrast model in overall populations and Asian (Overall: OR 1.303, 95%CI.: 1.031-1.648; Asian: OR 3.206, 95%CI.: 1.241-8.284), while no association was found in Caucasian (OR: 1.209; 95%CI.: 0.940-1.556). The results provided evidence for the association between the IL10 -1082G/A polymorphism and the risk of SLE. To confirm these findings, more case-control studies with subtle study design based on adequately sized populations are required.

The association between BANK1 and TNFAIP3 gene polymorphisms and systemic lupus erythematosus: a meta-analysis

The past decade has witnessed hundreds of reports declaring or not being able to replicable genetic association with systemic lupus erythematosus (SLE) susceptibility. BANK1 is a gene that encodes a B‐cell‐specific scaffold protein and its activation can affect B‐cell‐receptor‐induced calcium mobilization from intracellular calcium stores. TNFAIP3 encodes the ubiquitin‐modifying enzyme, also known as A20, which is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa‐B (NFKB) activity and tumour necrosis factor (TNF)‐mediated programmed cell death. The association of BANK1 and TNFAIP3 polymorphism with SLE has been reported in several studies. The aim of this study was to assess whether combined evidence shows the association between BANK1 and TNFAIP3 polymorphism and SLE. We report the results of a meta‐analysis of genome‐wide association scans and replication in independent sets for BANK1 and TNFAIP3 polymorphism and SLE that includes 12 416 subjects with SLE and 19 113 control subjects. Meta‐odds ratios (ORs) and 95% confidence intervals (CIs) based on random effects models. Both of BANK1 and TNFAIP3 harbour several controversial single nucleotide polymorphisms (SNPs). We selected and identified three SNPs of BANK1 associated with SLE (rs17266594, P = 1.949e‐10; OR = 1.380; 95% CI: 1.250–1.525; rs10516487, P = 2.642e‐13; OR = 1.317; 95% CI: 1.223–1.417; rs3733197, P = 3.452e‐06; OR = 1.193; 95% CI: 1.107–1.286); one SNP of TNFAIP3 associated with SLE (rs2230926, P = 1.502e‐12; OR = 1.826; 95% CI: 1.545–2.157). This meta‐analysis demonstrates a significant association between BANK1 and TNFAIP3 gene polymorphism and SLE in multiple ethnic populations. These findings reinforce the value of large sample series for discovery and follow‐up of genetic variants contributing to the aetiology of SLE.

Association of ITGAM polymorphism with systemic lupus erythematosus: a meta-analysis

Background  ITGAM is one of the major non‐human leucocyte antigen that has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The association of ITGAM polymorphism with SLE has been reported in several studies, but with inconclusive results.

Competitive endogenous RNA network: potential implication for systemic lupus erythematosus

ABSTRACT Introduction: Competitive endogenous RNA (ceRNA) hypothesis proposes that RNA transcripts, both coding and non-coding, crosstalk with and coregulate each other using microRNA response elements (MREs). CeRNA analysis tremendously expands functional information of coding and non-coding RNAs. Mounting evidence have shown that various types of RNAs, including pseudogenes, long non-coding RNAs, circular RNAs, and messenger RNAs, can function as ceRNAs in distinct physiological and pathophysiological states. Many validated ceRNA pairs participate in the initiation and progression of cancers, and systemic ceRNA network analyses revealing potential of ceRNAs in diagnosis, therapy, and prognosis of cancers have also been performed. Areas covered: This review concisely introduces ceRNA hypothesis and characteristics of ceRNA regulations. The major sections focus on representative examples of both protein coding and non-coding RNA transcripts acting as ceRNAs. CeRNA prediction programs and databases and implications of ceRNA network in cancers are then discussed. In the end, we surmise potential implications of ceRNA network for SLE. Expert opinion: The role of ceRNA network in systemic lupus erythematosus (SLE) remains undefined. We speculate that dissecting ceRNA network in SLE may help expand our comprehension of roles of transcriptome, particularly non-coding transcripts, and richen our knowledge of pathogenesis, diagnosis, and therapy of SLE.

Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases A Systematic Review and Meta-Analysis

We evaluated the differences in major markers of cardiovascular (CV) risk between inflammatory bowel diseases (IBDs) and controls by a systematic review and a meta-analysis. We searched PubMed, EMBASE, and Cochrane databases for literature comparing CV risk markers in IBDs and controls. The overall mean carotid intima-media thickness (CIMT), flow-mediated dilation (FMD%), and carotid-femoral pulse wave velocity (cfPWV) difference between patients with IBDs and control groups were calculated. Twenty-eight studies were included in the meta-analysis, including 16 studies with data on CIMT, 7 studies reporting FMD%, and 9 studies on cfPWV. Compared to controls, patients with IBDs showed significantly higher CIMT (standardized mean difference [ SMD]: 0.534 mm; 95% confidence interval [CI], 0.230 to 0.838; P = .001), significantly lower FMD% ( SMD, -0.721%; 95% CI, -1.020 to -0.421; P < .0001), and significantly increased cfPWV ( SMD, 0.849; 95% CI, 0.589 to 1.110; P < .0001). When analyzing subgroups with ulcerative colitis and Crohn disease (CD), all results were still significant except CIMT in CD. Our findings support the current evidence for an elevated CV burden in patients with IBD and support the clinical utility of markers of subclinical atherosclerosis in the management of these patients.

Prevalence and factors associated with late HIV diagnosis

While highly active antiretroviral therapy has been successful in delaying progression into AIDS, late HIV diagnosis remains a major contributor to the mortality and morbidity of AIDS. An epidemiological study was conducted to evaluate the prevalence and factors of late diagnosis and the characteristics of those individuals with late diagnosis in Liuzhou city. Patients with late diagnosis were defined as either those who were diagnosed with AIDS at the time of HIV diagnosis or as those who developed AIDS no more than 1 year after HIV diagnosis. Of 899 participants, 72.6% had a late diagnosis. Common characteristics of those who experienced late diagnosis included older participants, those who were unexpectedly diagnosed while seeking other medical attention, participants who believed they could not acquire HIV from their regular heterosexual partners, those who never considered getting tested for HIV, and patients with unexplained weight loss, angular cheilitis, or prolonged fever prior to HIV diagnosis. On the other hand, those participants who were diagnosed via testing at compulsory rehabilitation centers and those whose annual household income was greater than 30,000 Yuan were less likely to be diagnosed late. These results suggested that late HIV diagnosis is common in Liuzhou city, and it is essential to promote appropriate strategies to detect HIV infections earlier. Strategies that require HIV/AIDS patients to notify their spouse/sexual‐partners about their HIV‐positive results within one month and start provider‐initiated HIV testing and counseling in medical facilities are beneficial to earlier HIV diagnosis. J. Med. Virol. 87:970–977, 2015.

D18S880 microsatellite polymorphism of carnosinase gene and diabetic nephropathy: a meta-analysis.

OBJECTIVE The aim of this study was to determine whether the CNDP1 (carnosinase gene) D18S880 microsatellite polymorphism confers susceptibility to diabetic nephropathy (DN). METHODS The authors conducted meta-analysis on association between the CNDP1 D18S880 microsatellite polymorphism and DN susceptibility, using fixed and random effects models. RESULTS A total of nine comparative studies were included in this meta-analysis, which included 4546 DN, 7994 diabetes mellitus (DM), and 1826 healthy (Heal) subjects. Overall, the analysis revealed that the D18S880 microsatellite polymorphism was significantly associated with DN for the five trinucleotide repeat (5L) allele and five leucines repeat (5L-5L) homozygous in the comparisons of DN versus DM (5L: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.84-0.97, p=0.008; 5L-5L: OR 0.88, 95% CI 0.81-0.97, p=0.006) and DN versus non-DN (DM+Heal) (5L: OR 0.92, 95% CI 0.86-0.98, p=0.009; 5L-5L: OR 0.89, 95% CI 0.82-0.96, p=0.004). The protective effects of the D18S880 polymorphism were similar to those observed in the subgroups of the type 2 DM and the Caucasian population. However, significant association was not found in the type 1 DM population. CONCLUSIONS This meta-analysis confirms that the carnosinase D18S880 microsatellite polymorphism is associated with DN susceptibility, especially in the type 2 DM and the Caucasian population.

Translation of noncoding RNAs: Focus on lncRNAs, pri-miRNAs, and circRNAs

Abstract Mammalian genome is pervasively transcribed, producing large number of noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), primary miRNAs (pri‐miRNA), and circular RNAs (circRNAs). The translation of these ncRNAs has long been overlooked. Increasing studies, however, based on ribosome profiling in various organisms provide important clues to unanticipated translation potential of lncRNAs. Moreover, a few functional peptides encoded by lncRNAs and pri‐miRNAs underline the significance of their translation. Recently, several novel researches also evidence the translation of endogenous circRNAs. Given the functional significance exemplified by peptides translated by some ncRNAs and their pervasive translation, it is not too far‐fetched to image that abnormal translation of ncRNAs may contribute to human diseases. Through challenging, deciphering ncRNA translation is required for comprehensive understanding of biology and medicine. In this review, we firstly present evidence concerning translation potential of lncRNAs and go on to introduce a few functional short peptides encoded by lncRNAs. Then, salient observations showing translation of pri‐miRNAs and circRNAs are described in detail. We end by discussing the impact of ncRNA translation beyond producing peptides and referring briefly to the potential role of abnormal ncRNA translation in human diseases. HighlightsMethods based on ribosome profiling highlight translation potential of lncRNAs.Peptides encoded lncRNAs and pri‐miRNAs display functional importance.Translation of endogenous circRNAs has recently been discovered.The role of abnormal translation of ncRNAs in human disorders merits further investigation.