Shared genetic architecture between type 2 diabetes and COVID-19 severity.

PURPOSE: Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. RESULTS: Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization (rg = 0.156, SE = 0.057, p = 0.005) or severe disease (rg = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having pgene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. CONCLUSIONS: Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets.

[Clinical research of a continuous auscultation recorder based on artificial intelligence].

Objective: To investigate the feasibility and clinical significance of a continuous auscultation recorder of bowel sounds based on artificial intelligence in monitoring the bowel sounds. Methods: From November 1,2018 to August 12,2019, a continuous auscultation recorder of bowel sounds was applied to monitor the perioperative bowel sounds of 31 patients undergoing colorectal surgery, in order to discovery underlying rules which might be used to guide clinical practice. Results: After the operation, the bowel sounds continued to exist for (1.8±0.8) h, and then gradually weakened or disappeared, and recovered gradually after (11.2±3.5) h. The first exhaust and the first defecation were detected at the time of (22.7±5.8) h and (28.7±6.9) h after surgery, respectively. The bowel sounds rate increased after eating, and decreased significantly after exhaust/defecation. Conclusions: The continuous auscultation recorder of bowel sounds based on artificial intelligence was safe and effective, which can afford help to clinical evaluation.

Effect of air pollution on hospital admissions for systemic lupus erythematosus in Bengbu, China: a time series study.

Recently, exposure to air pollutants has been associated with the development and progression of systemic lupus erythematosus (SLE). The current study aims to evaluate the effects of air pollutants on SLE hospital admissions in Bengbu, China. We performed distributed lag non-linear model combined with quasi-Poisson generalized linear regression to assess the impacts of air pollutants on SLE admissions from 2015 to 2017. Subgroup analyses by admission status (first admission or readmission) were also evaluated. A total of 546 hospital admissions during 2015-2017 were included. For single-day lag structures, the risk effects occurred from lag 2 to lag 9 for the 75th percentile particulate matter (PM)2.5, lag 3 to lag 9 for the 80th percentile PM2.5. For cumulative lag structures, the risk effects occurred from lag 0-5 to lag 0-14 for both 75th PM2.5 and 80th PM2.5, and no significant effect was observed for 90th PM2.5. In addition, the adverse effects on SLE first admissions occurred from lag 0 to lag 1 for NO2, lag 1 to lag 2 for SO2. The maximum effect of PM2.5 on SLE was 4.27 (95% confidence interval: 1.34-13.59) at lag 0-13 day, the minimum effect value was 1.12 (95% confidence interval: 1.03-1.23) at lag 9 day. These findings demonstrate that high PM2.5, NO2 and SO2 are associated with SLE hospital admissions. In addition, this study further revealed that exposure to high concentration of PM2.5 increased the risk of SLE relapse, while high levels of NO2 and SO2 increased the risk of SLE first admissions.

Plasma melatonin levels do not differ in SLE patients.

OBJECTIVE: This study aims to investigate the plasma melatonin levels in systemic lupus erythematosus (SLE) patients and its relationship with clinical and laboratory features. PATIENTS AND METHODS: A total of 90 patients with SLE (82 females, 8 males; mean age 37.86 ± 13.98 years, range 19-77 years) and 90 healthy controls (82 females, 8 male; mean age 36.54 ± 10.89 years, range 22-60 years) were recruited for the current study. Plasma melatonin levels were detected by enzyme-linked immunosorbent assay. RESULTS: Melatonin levels were not significantly different in the plasma of patients with SLE compared with controls (P = 0.026). There was no significant difference regarding plasma melatonin level between SLE patients with nephritis and those without nephritis (P = 0.714); no significant difference was found between less active SLE and more active SLE (P = 0.791). The presence of IgM was associated with melatonin levels (P = 0.031) in SLE patients. CONCLUSIONS: There is no significant difference in plasma melatonin levels between SLE patients and controls. Further studies are needed to elucidate the role of melatonin in SLE.

Association between IRAK1 rs3027898 and miRNA-499 rs3746444 polymorphisms and rheumatoid arthritis : A case control study and meta-analysis.

BACKGROUND: The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent. AIM: A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. MATERIAL AND METHODS: A total of 386 RA patients were enrolled along with 576 matched healthy controls. Genotyping was performed by using TaqMan genotyping assays on Fluidigm 192.24 system. For the meta-analysis, a systematic literature search was conducted to identify all relevant studies. RESULTS: This case control study showed that the IRAK1 rs3027898 C allele was associated with increased risk of RA with an odds ratio (OR) = 1.4 and 95 % confidence intervals (CI) = 1.093-1.793, P = 0.008 but miR-499 rs3746444 polymorphisms were not significantly associated with the risk for RA. The meta-analyses included a total of 4 case control studies on IRAK1 rs3027898 and 4 studies on miR-499 rs3746444. The IRAK1 rs3027898 C allele had an overall OR of 1.268 (95 % CI = 1.130-1.424, P < 0.001). After stratification by ethnicity the C allele had an OR of 1.238 (95 % CI = 1.096-1.398, P = 0.001) in Asians. No association between miR-499 rs3746444 polymorphism and RA was found in the overall and Asian populations. CONCLUSION: The results from our case control study and the meta-analyses indicate that the IRAK1 rs3027898 C allele is significantly associated with an increased risk of RA, especially in Asians.

Epidemiological characteristics and influential factors of hand, foot and mouth disease (HFMD) reinfection in children in Anhui province.

Hand, foot and mouth disease (HFMD) is an acute contagious condition caused by a spectrum of human enteroviruses. HFMD reinfection is common in the absence of cross-protection from other virus subtypes. This study focused on reinfection in children in Anhui province, China between 2008 and 2013 using surveillance system data. We classified 8960 cases as reinfected, corresponding to a rate of 2·02%. The reinfection rate was higher in boys than in girls [odds ratio (OR) 1·27, 95% confidence interval (CI) 1·21-1·32, P < 0·001], children aged < 3 years (OR 3·82, 95% CI 3·58-4·07, P < 0·001), and children living in rural areas (OR 1·09, 95% CI 1·04-1·14, P = 0·001). The reinfection rate in children who were originally infected with non-enterovirus A71 (non-EVA71) enteroviruses was higher than those infected with EVA71 (OR 1·36, 95% CI 1·02-1·80, P = 0·034). Influential factors of reinfection rate included annual incidence (ß coefficient = 0·715, P = 0·002) and the proportion of EVA71 in patients with mild HFMD (ß coefficient = -0·509, P = 0·018). These results demonstrate that boys aged <3 years, especially those in rural areas or regions with a lower EVA71 proportion are more prone to reinfection, and specific health education programmes should be developed to protect these susceptible populations.

Decreased serum levels of T-cell immunoglobulin mucin-1 and T-cell immunoglobulin mucin-3 in systemic lupus erythematosus patients.

This study aims to investigate the serum T-cell immunoglobulin mucin (TIM)-1 and TIM-3 levels in systemic lupus erythematosus (SLE) patients and analyze their correlations with clinical features. Sixtyone SLE patients and 69 healthy controls were enrolled, serum TIM-1 and TIM-3 levels were detected by ELISA. Results demonstrated that both serum TIM-1 and TIM-3 levels were significantly decreased in SLE patients compared with controls (both P less than 0.05). Lower serum TIM-3 levels in SLE patients with nephritis were observed when compared to those without nephritis, with a marginal statistical significance (P=0.059). However, both serum TIM-1 and TIM-3 levels had no significant correlation with SLE disease activity (both >0.05). In summary, decreased serum TIM-1 and TIM-3 levels and association of TIM-3 with nephritis suggest their possible role in the development and pathogenesis of SLE. However, further studies are needed to confirm these preliminary results.

Transcriptome analysis of peach (Prunus persica L. Batsch) during the late stage of fruit ripening.

Fruit ripening is a complex developmental process, the details of which remain largely unknown in fleshy fruits. In this paper, the fruit flesh of two peach varieties, "Zhongyou9" (a nectarine; Prunus persica L. Batsch) and its mutant "Hongyu", was analyzed by RNA-seq technology during two stages of ripening at 20-day intervals. One hundred and eighty significant upregulated and two hundred and thirty-five downregulated genes were identified in the experiment. Many of these genes were related to plant hormones, chlorophyll breakdown, accumulation of aroma and flavor volatiles, and stress. To the best of our knowledge, this is the first transcriptome analysis of peach ripening, and our data will be useful for further studies of the molecular basis of fruit ripening.

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

OBJECTIVE: 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. METHODS: A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association. RESULTS: A total of 6001 cases and 6788 controls from 24 studies were analysed. Significant association of the C allele of IL-4 rs2243250 polymorphism with rheumatoid arthritis (RA) was detected (odds ratio (OR) = 0.696, 95% confidence interval (CI) = 0.601-0.807). Stratification by ethnicity indicated an association between the IL-4 rs2243250 polymorphism and RA in Caucasians. Furthermore, the overall ORs of the associations between the C allele and multiple scleorosis (MS) were 1.340 (95% CI = 1.102-1.630). However, we failed to reveal any association between IL-4 rs2243250 polymorphism and systemic lupus erythematosus (SLE), type 1 diabetes (T1D) or Graves' disease (GD). CONCLUSIONS: The present study suggests that the IL-4 rs2243250 polymorphism might be associated with genetic susceptibility to autoimmune diseases, including RA and MS.

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.

Serum levels of cytokines in systemic lupus erythematosus : Association study in a Chinese population.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. The clear pathogenesis of SLE has not been fully elucidated. Cytokine-mediated immunity has been showed to be involved in the pathogenesis of SLE. OBJECTIVES: The aim of this study was to investigate serum levels of cytokines (IL-19, IL-24, IL-26, IL-31, IL-32, IL-36) in SLE patients, in comparison with normal controls in a Chinese population. MATERIALS AND METHODS: A total of 65 patients with SLE and 65 healthy volunteers were recruited for the current study. All serum levels of cytokines were measured by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not significantly different from the normal controls (all p > 0.05). CONCLUSION: Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not markedly different from the normal controls. However, functional research should be discussed in future studies to elucidate the roles of these cytokines in SLE.

A bibliometric study of literature on SLE research in PubMed (2002-2011).

OBJECTIVE: The objective of this paper is to study the distribution regularity, development tendency and research hot spots of systemic lupus erythematosus (SLE) literature published in journals indexed in PubMed over a 10-year period using the bibliometric analysis method. METHODS: Citations from 2002 to 2011 were downloaded from the PubMed database. The core of the search was the Medical Subject Headings (MeSH) "Lupus Erythematosus, Systemic." The period of study was set from 2002 to 2011. RESULTS: A total of 14,053 articles were retrieved. These articles were published in 1627 different journals, nine journals contributing to one-third of all the literature. The first three journals containing the most articles were CONCLUSION: SLE has become a field of interest over the period 2002 to 2011. However, lupus research publications in developing countries have lagged behind.

MicroRNA-101, mitogen-activated protein kinases and mitogen-activated protein kinases phosphatase-1 in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is the prototype of human autoimmune disease in which various inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-6 and interferon (IFN) play crucial pathogenic roles. The production of these cytokines is responsible for the mitogen-activated protein kinases (MAPKs), which can also generate mitogen-activated protein kinases phosphatases (MKPs). MKP-1, a prototypical member of the MKP family that can influence outcomes of autoimmune diseases and reduce the inflammatory cytokines by dephosphorylation of p38 and JNK MAPK, plays a critical role in the expression of inflammatory mediators at transcriptional and post-transcriptional levels. MicroRNA-101 (miR) is a small non-coding RNA that regulates the MAPK response by targeting MKP-1 mRNA 3'-UTR, and affects the secretion of the downstream inflammatory cytokines. However, the interaction among the above three in the pathogenesis of SLE has not previously been reported. This review discusses the current understanding of the role of the MAPK/MKP/miR-101 axis in regulating immune responses and the pathogenesis of SLE to provide new ideas for clinical treatment of SLE.

Association of the interleukin-10 gene polymorphism (-1082A/G) with systemic lupus erythematosus: a meta-analysis.

OBJECTIVE: The interleukin-10 (IL-10) gene polymorphism (-1082A/G) has been shown to be associated with systemic lupus erythematosus (SLE), but findings are not consistent across studies. The aim of our meta-analysis was to assess the association between the -1082A/G polymorphism in the IL-10 gene and SLE. METHODS: We searched all publications on the association between the IL-10 (-1082A/G) polymorphism and SLE in PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese). Meta-analysis was conducted using software Stata version 10.1. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed-/random-effects models depended on Cochran's Q-statistic and I(2) values. RESULTS: A total of 17 studies with 2396 cases and 3653 controls were included in this meta-analysis. Meta-analysis was performed for genotypes GG versus AA, GG + AG versus AA, GG versus AG + AA, and G allele versus A allele. Significant differences were found in genotype distribution between SLE and normal controls in whole-population GG versus AA (OR = 1.428, 95% CI = 1.006-2.208). Similar results were detected in the dominant genetics effect of the G allele (OR = 1.202, 95% CI = 1.030-1.403). No significant association was found in allele distribution in whole-population G versus A (OR = 1.125, 95% CI = 0.998-1.269). In subgroup analysis by ethnicity, significant association was found when GG + AG versus AA was performed in a European population (OR = 1.240, 95% CI = 1.022-1.503) and GG versus AG + AA was performed in an Asian population (OR = 3.596, 95% CI = 1.389-9.311). Significant association was found between genotype distribution in Asians (OR = 4.491, 95% CI = 1.552-13.000). Publication year was detected as the source of heterogeneity. In the stratified analysis by publication year, the pooled OR was 1.049 (95% CI = 0.940-1.171; P (heterogeneity) = 0.431; I(2) ( )= 0.4%) in subgroup 1 (publication years 1999-2004). No significant association was found between the IL-10 (-1082 G) allele and SLE in subgroup 1 (Z = 0.85, p = 0.431). In subgroup 2 (publication years 2005-2011), the pooled OR was 1.327 (95% CI = 1.125-1.565; P (heterogeneity) = 0.143; I(2) ( )= 35.8%). Significant association was found between the IL-10 (-1082 G) allele and SLE (Z = 3.36, p = 0.001). CONCLUSIONS: This meta-analysis demonstrates the association between the IL-10 (-1082A/G) polymorphism and SLE. However, further studies are needed for a definitive conclusion.

Sex-specific differences in the relationship between the single-nucleotide polymorphism rs2298804 of FCER1A and the susceptibility to systemic lupus erythematosus in a Chinese Han population.

BACKGROUND: IgE plays a important role in systemic lupus erythematosus (SLE). A recent study identified the high-affinity IgE receptor α-chain (FcεRIα) gene FCER1A as a susceptibility locus influencing total serum IgE levels. AIM: To investigate whether the single-nucleotide polymorphism (SNP) rs2298804 (251 A>G) of FCER1A is associated with SLE and its clinical characteristics in a Chinese Han population. METHODS: This case-control study enrolled 948 patients with SLE and 976 healthy controls. Precise phenotyping of patients was accomplished by means of a questionnaire and clinical examination. rs2298804 was genotyped using real-time fluorescence quantitative PCR. RESULTS: Compared with the healthy controls, patients with SLE had much lower frequencies of the AG genotype (OR = 0.26; 95% CI 0.194-0.374; P << 0.001) and G allele (OR = 0.45; 95% CI 0.36-0.55; P << 0.001). We also found a stronger association of the FCER1A exon SNP, rs2298804 (A/G), in females (OR = 0.42; 95%CI 0.34-0.53; P << 0.001) compared with males (OR = 0.52; 95% CI 0.28-0.97; P < 0.04). G-allele carriers are less likely to develop SLE than A-allele carriers. Although we did not find any significant correlation between the rs2298804 and the incidence of lupus nephritis, rs2298804 seemed to protect against proteinunia, fever and hypocomplementaemia in patients with SLE, but appeared to be a risk factor for photosensitivity and vasculitis. CONCLUSIONS: We found that rs2298804 seemed to have a protective effect against SLE in Chinese patients, especially women. It also protected against proteinunia, fever and hypocomplementaemia, but was a risk factor for photosensitivity and vasculitis.

Association of CD247 with systemic lupus erythematosus in Asian populations.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

Lack of association between CTLA-4 +49A/G and -318C/T polymorphisms and Behçet's disease risk: a meta-analysis.

OBJECTIVES: To more precisely determine whether there is a significant association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms with the susceptibility for Behçet's disease. METHODS: Eight studies that included data from 7 articles were identified using PubMed, Embase, Chinese Biomedical Literature Database (CBM), and Chinese National Knowledge Infrastructure (CNKI) published before March 2012. Meta-analysis was performed for two CTLA-4 gene polymorphisms, +49A/G (rs231775) and -318C/T (rs5742909). Statistical analyses were performed using software Review Manager (version 5.1) and Stata (version 11.0). The pooled odds ratio (OR) with 95% confidence interval (95%CI) were presented. RESULTS: Overall, no significant association was detected in all genetic models when all studies were pooled into the meta-analysis (for +49A/G polymorphism: A vs. G, OR=1.173, 95% CI=0.790-1.743; A/A vs. A/G+G/G, OR=1.422, 95% CI=0.718-2.814; A/A+A/G vs. G/G, OR=1.421, 95% CI=0.729-2.767; and for -318C/T polymorphism: C vs. T, OR=1.051, 95% CI=0.844-1.307; C/C vs. T/T+C/T, OR=1.154 95% CI=0.891-1.495, C/C+C/T vs. T/T, OR=1.044, 95% CI=0.301-3.617). Furthermore, in the subgroup analysis by ethnicity, there was also lack of evidence for the association in Turkish patients. CONCLUSIONS: Our study failed to provide evidence for the genetic association between CTLA-4 +49A/G and -318C/T polymorphisms with Behçet's disease based on currently available evidence from literature. Further confirmations in large and well-designed studies including other CTLA-4 gene polymorphisms are needed.

Lack of association of interleukin-18 gene promoter -607 A/C polymorphism with susceptibility to autoimmune diseases: a meta-analysis.

OBJECTIVE: Published data on the association between interleukin (IL)-18 gene promoter -607 A/C polymorphism and autoimmune diseases risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS: A total of 17 studies, including six studies on type 1 diabetes (T1D), four on rheumatoid arthritis (RA), five on systemic lupus erythematosus (SLE), three on Crohn's Disease (CD) and three on ulcerative colitis (UC), were available for the meta-analysis. Meta-analysis was performed for genotypes A/A (recessive effect), genotypes A/A + A/C (dominant effect), and A allele in fixed or random-effects models. RESULTS: Overall, no significantly elevated autoimmune diseases risk was found in all genetic models when all studies were pooled into the meta-analysis. The overall odds ratios (ORs) and 95% confidence intervals (CIs) for A-allele were T1D (OR = 0.938, 95% CI = 0.757-1.162), RA (OR = 0.759, 95% CI = 0.540-1.067), SLE (OR = 0.858, 95% CI = 0.609-1.208), CD (OR = 1.159, 95% CI = 0.975-1.379) and UC (OR = 1.170, 95% CI = 0.977-1.402), respectively. In the subgroup analysis by ethnicity, there was still no significant association detected in all genetic models. CONCLUSIONS: To date, there is still not enough evidence to indicate the association of IL-18 gene promoter -607 A/C polymorphism and the development of autoimmune diseases.

Ets-1: a new player in the pathogenesis of systemic lupus erythematosus?

v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) (Ets-1) is a member of the Ets family of transcription factors that share a unique Ets DNA binding domain. They control a wide variety of cellular processes including cell proliferation and differentiation. Recently, two genome-wide association studies in systemic lupus erythematosus (SLE) independently identified genetic variants in Ets-1 associated with SLE. Interestingly, previous studies have found that Ets-1-deficient mice develop lupus-like disease characterized by high titers of IgM and IgG autoantibodies, immune complex-mediated glomerulonephritis, and local activation of complement. In addition, Ets-1 is also involved in many cellular abnormalities that are known to participate in SLE pathogenesis, such as its role in negative regulation of Th17 cell and B cell differentiation. All these findings suggest that Ets-1 may play an important role in the pathogenesis of SLE. This article will focus on current understanding of the role of Ets-1 in the physiological and pathological functions associated with SLE. It is the intention of the article to provide insights which may assist in the development of Ets-1 based approaches for the treatment 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. OBJECTIVES: The aim of this study was to assess whether combined evidence shows the association between ITGAM polymorphism and SLE. METHODS: A meta-analysis was performed to survey studies on the ITGAM polymorphism and SLE using comprehensive Medline search and review of the references. A total of five published studies including 12,123 patients with SLE and 17,016 controls were involved. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed effects models or random effects models were depended on Cochran's Q-statistic and I(2) values. RESULTS: The overall ORs for the minor A-allele (OR 1.795; 95%CI 1.676-1.921), AA vs. GG (OR 3.540; 95%CI 2.771-4.522), AG vs. GG (OR 1.750; 95%CI 1.617-1.895), dominant model (OR 1.857;95%CI 1.719-2.005), recessive model (OR 3.041; 95%CI 2.384-3.878) of ITGAM rs1143679 were significantly increased in SLE and fixed effects models were conducted. All controls were in Hardy-Weinberg (HW) proportion. Although this meta-analysis showed significant association of rs1143683 (A vs. G, OR 1.534;95%CI 1.312-1.792), rs9888739 (T vs. C,OR 1.627;95%CI 1.380-1.918), rs1143678 (T vs. C, OR 1.543; 95%CI 1.330-1.790), rs9937837 (A vs. G, OR 0.466; 95%CI 0.227-0.957) with SLE; all of these were conducted in random effects model as heterogeneity was detected. No significant association was detected in the analysis between rs11574637 and SLE. No publication bias was presented. CONCLUSIONS: This meta-analysis demonstrates a significant association between ITGAM gene polymorphism and SLE in multiple ethnic populations.