Association Between Interleukin 35 Gene Single Nucleotide Polymorphisms and the Uveitis Immune Status in a Chinese Han Population

Autoimmune uveitis is characterized by immune disorders of the eyes and the whole body and is often recurrent in young adults, but its pathogenesis is still unclear. IL-35 is an essential regulatory factor in many autoimmune diseases, which is produced by Breg cells and can induce Breg cells to regulate the immune response. The relationship between the expression and gene polymorphism of IL-35 and the immune status of patients with autoimmune uveitis has not been reported. The peripheral blood of the subjects was collected from patients with Behçet’s Disease (BD) and those with Vogt–Koyanagi–Harada (VKH) syndrome. The percentage of immune cell subsets including B cells, DC, and T cells, and the expression of IL-35 in serum of these two kinds of disease were analyzed. And then, the associations between seven IL-35 single nucleotide polymorphism (SNP) sites and disease susceptibility, the immune status, the clinical characteristics, and the serum IL-35 levels were analyzed. Our results showed that the percentage of Breg cells was significantly decreased in the blood of patients with VKH syndrome compared to that of healthy controls. The levels of IL-35 in the serum of patients with VKH syndrome or BD patients were not changed significantly, compared to that of healthy controls. Furthermore, the associations between two subunits of IL-35 (IL-12p35 and EBI3) and BD or VKH patients were analyzed. We found that there was an association between the EBI3 rs428253 and the occurrence of BD. There was an association between the IL-12p35 rs2243131 and the low level of Breg cell of VKH patients. In addition, there were associations between the polymorphisms of EBI3 rs4740 and the occurrence of headache and tinnitus of VKH patients, respectively. And the genotype frequency of IL-12p35 rs2243115 was related to the concentration of serum IL-35 in patients with VKH syndrome. Thus, the specific SNP sites change of IL-35 were correlated to the immune disorders in uveitis. And they may also play a guiding role in the occurrence of clinical symptoms in patients with uveitis, especially for VKH syndrome.

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Association of Plasma IL-32 Levels and Gene Polymorphisms with Systemic Lupus Erythematosus in Chinese Han Population

Disease Markers ◽

10.1155/2016/2460206 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Yanyun Wang ◽

Bin Zhou ◽

Yi Zhao ◽

Xiuzhang Yu ◽

Yi Liu ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Gene Polymorphisms ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Systemic Lupus ◽

Chinese Han ◽

Single Nucleotide ◽

Published Report ◽

The Relationship

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. IL-32, a secreted protein, has been reported to be associated with several autoimmune diseases. Our preliminary experiment showed different plasma IL-32 levels than that mentioned in a published report on the same population. In order to elucidate the correlation between IL-32 and SLE, we determined the plasma level and two single nucleotide polymorphisms (SNPs) of IL-32 in 152 patients with SLE and 310 healthy controls and analyzed the relationship based on the clinical parameters. The results showed that plasma IL-32 levels in patients with SLE were markedly lower than that in the healthy controls. In the SLE group, patients with detectable IL-32 presented low serum C3 concentrations. Further studies indicated that the rs28372698 SNP was associated with the susceptibility to SLE. Taken together, our results suggested that IL-32 could possibly be a candidate marker to monitor SLE disease stability and screening in future.

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Associations of Polymorphisms inHRH2,HRH3,DAO,andHNMTGenes with Risk of Chronic Heart Failure

BioMed Research International ◽

10.1155/2016/1208476 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Gong-Hao He ◽

Wen-Ke Cai ◽

Jia-Bin Zhang ◽

Chao-Yu Ma ◽

Feng Yan ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Histamine Level ◽

Additive Models ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Clinical Associations ◽

First Time

The pathophysiological functions of cardiac histamine level and related histamine receptors during the development of chronic heart failure (CHF) were intensively investigated previously. However, the relevance of polymorphisms in histamine-related genes, such asHRH2,HRH3,DAO,andHNMT, with CHF remains largely neglected. This study herein aims to analyze the clinical associations of polymorphisms in those genes with CHF risk. A total of 333 unrelated Chinese Han CHF patients and 354 ethnicity-matched healthy controls were recruited and 11 single nucleotide polymorphisms (SNPs) were genotyped. We found that theHRH3rs3787429 polymorphism was associated with CHF risk (p<0.001). The T allele of rs3787429 exhibited protective effect against CHF under the dominant (ORs = 0.455; 95% CIs = 0.322–0.642) and additive models (ORs = 0.662; 95% CIs = 0.523–0.838), while, for SNPs inHRH2,DAO,andHNMT, no significant associations were observed in the present study. These findings for the first time screen out one SNP (rs3787429) ofHRH3gene that was significantly associated with CHF in Chinese Han population, which may be a novel biomarker for personal prevention and treatment of CHF and provides novel highlights for investigating the contribution of this disease.

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Genetic variation of SMAD3 is associated with hip osteoarthritis in a Chinese Han population

Journal of International Medical Research ◽

10.1177/0300060517745186 ◽

2018 ◽

Vol 46 (3) ◽

pp. 1178-1186 ◽

Cited By ~ 4

Author(s):

Fuhua Zhong ◽

Jianwei Lu ◽

Yangxin Wang ◽

Hongpu Song

Keyword(s):

Genetic Variation ◽

Hip Osteoarthritis ◽

Chinese Han Population ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Han Population ◽

Healthy Control ◽

Stratified Analysis

Objective This study was performed to investigate the association between genetic variation in SMAD3 and hip osteoarthritis (OA) in a Chinese Han population. Methods The frequency of two single nucleotide polymorphisms of SMAD3, rs1470002 and rs12901499, was examined in 500 patients with hip OA and 1080 healthy controls in a Chinese Han population. Further analysis was performed according to sex and age. Results We detected statistically significant differences in the allele frequency and genotype between the hip OA and healthy control groups. The frequency of the GA+GG and GA genotypes of rs12901499 and the G variant were much higher in patients with hip OA than in healthy controls. This association was also present when the participants were stratified by sex and age. However, there was no significant association between the risk of hip OA and the presence of rs1470002 GA, AA, or GA+AA genotypes, even after sex- and age-stratified analysis. Conclusions The SMAD3 SNP rs12901499 GA genotype and G variant may increase the risk of hip OA in Chinese Han patients.

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Positive Association betweenANKRD55Polymorphism 7731626 and Dermatomyositis/Polymyositis with Interstitial Lung Disease in Chinese Han Population

BioMed Research International ◽

10.1155/2017/2905987 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Liubing Li ◽

Si Chen ◽

Xiaoting Wen ◽

Qian Wang ◽

Guanting Lv ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Single Nucleotide Polymorphisms ◽

Lung Disease ◽

Positive Association ◽

Chinese Han Population ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Han Population

Single nucleotide polymorphisms (SNPs) inTNFSF4andANKRD55genes have been shown to be associated with several autoimmune diseases, although whether these genes are susceptibility genes for dermatomyositis/polymyositis (DM/PM) has, to date, not been reported. This study aimed to investigate the potential associations of these SNPs with DM/PM in a Chinese Han population. Five SNPs inTNFSF4(rs2205960, rs844644, and rs844648) andANKRD55(rs6859219, rs7731626) genes were genotyped using the SequenomMassArray system in 2297 Chinese individuals. In total, 1017 DM/PM patients and 1280 gender-matched healthy controls were genotyped. No significant associations were observed in DM/PM patients for the five SNPs analyzed. The association between SNPs and interstitial lung disease (ILD) was also investigated. Both DM-ILD (Pc=0.030, OR = 0.65, 95% CI: 0.47–0.88) and DM/PM-ILD (Pc= 0.015, OR = 0.67, 95% CI: 0.51–0.87) exhibited a significant association with the rs7731626-A allele. Rs7731626-A was less frequently found in DM-ILD and DM/PM-ILD patients compared with healthy controls. This is the first study to demonstrate a positive association betweenANKRD55polymorphism and DM-ILD and DM/PM-ILD. A decreased frequency of rs7731626-A in DM-ILD and DM/PM-ILD patients suggests that the A variant may be protective against DM/PM-ILD.

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Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population

European Journal of Ophthalmology ◽

10.1177/11206721211002698 ◽

2021 ◽

pp. 112067212110026

Author(s):

Pablo Gili ◽

Leyre Lloreda Martín ◽

José-Carlos Martín-Rodrigo ◽

Naon Kim-Yeon ◽

Laura Modamio-Gardeta ◽

...

Keyword(s):

Macular Degeneration ◽

Gene Polymorphisms ◽

Age Related Macular Degeneration ◽

Spanish Population ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Exudative Amd ◽

Age Related ◽

Increased Risk

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.

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OP0286 PROTEOMICS AND RNA SEQUENCING APPROACHES HIGHLIGHT THE ROLE OF ENDOTHELIAL CELL DYSREGULATION IN IL-1 AND IFN MEDIATED AUTOINFLAMMATORY DISEASES, NOMID AND CANDLE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.351 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 178-179

Author(s):

S. Alehashemi ◽

M. Garg ◽

B. Sellers ◽

A. De Jesus ◽

A. Biancotto ◽

...

Keyword(s):

Endothelial Cell ◽

Whole Blood ◽

Cell Activation ◽

Immune Cell ◽

Differentially Expressed ◽

Neutrophilic Dermatosis ◽

Healthy Controls ◽

Differentially Expressed Proteins ◽

Rna Seq ◽

Before And After

Background:Systemic Autoinflammatory diseases present with sterile inflammation. NOMID (Neonatal-Onset Multisystem Inflammatory Disease) is caused by gain-of-function mutations inNLRP3and excess IL-1 production, presents with fever, neutrophilic dermatosis, aseptic meningitis, hearing loss and eye inflammation; CANDLE (Chronic Atypical Neutrophilic Dermatosis, Lipodystrophy and Elevated Temperature) is caused by loss-of-function mutations in proteasome genes that lead to type-1 interferon signaling, characterized by fever, panniculitis, lipodystrophy, cytopenia, systemic and pulmonary hypertension and basal ganglia calcification. IL-1 blockers are approved for NOMID and JAK-inhibitors show efficacy in CANDLE treatment.Objectives:We used proteomic analysis to compare differentially expressed proteins in active NOMID and CANDLE compared to healthy controls before and after treatment, and whole blood bulk RNA seq to identify the immune cell signatures.Methods:Serum samples from active NOMID (n=12) and CANDLE (n=7) before and after treatment (table 1) and age matched healthy controls (HC) (n=7) were profiled using the SomaLogic platform (n=1125 proteins). Differentially expressed proteins in NOMID and CANDLE were ranked after non-parametric tests for unpaired (NOMIDp<0.05, CANDLE,p<0.1) and paired (p<0.05) analysis and assessed by enriched Gene Ontology pathways and network visualization. Whole blood RNA seq was performed (NOMID=7, CANDLE=7, Controls =5) and RPKM values were used to assess immune cells signatures.Table 1.Patient’s characteristicsNOMIDN=12, Male =6CANDLEN=7, Male =6AgeMedian (range)12 (2, 28)16 (3, 20)Ethnicity%White (Hispanic)80 (20)100 (30)GeneticsNLRP3mutation(2 Somatic, 10 Germline)mutations in proteasome component genes(1 digenic, 6 Homozygous/compound Heterozygous)Before treatmentAfter treatmentBefore treatmentAfter treatmentCRPMedian (range) mg/L52 (16-110)5 (0-23)5 (0-101)1 (0-4)IFN scoremedian (range)0NA328 (211-1135)3 (0-548)Results:Compared to control, 205 proteins (127 upregulated, 78 downregulated) were significantly different at baseline in NOMID, compared to 163 proteins (101 upregulated, and 62 downregulated) in CANDLE. 134 dysregulated proteins (85 upregulated, 49 downregulated) overlapped in NOMID and CANDLE (Figure 1). Pathway analysis identified neutrophil and monocyte chemotaxis signature in both NOMID and CANDLE. NOMID patients had neutrophilia and active neutrophils. CANDLE patients exhibited active neutrophils in whole blood RNA. Endothelial cell activation was the most prominent non-hematopoietic signature and suggest distinct endothelial cell dysregulation in NOMID and CANDLE. In NOMID, the signature included neutrophil transmigration (SELE) endothelial cell motility in response to angiogenesis (HGF, VEGF), while in CANDLE the endothelial signatures included extracellular matrix protein deposition (COL8A) suggesting increased vascular stiffness. CANDLE patients had higher expression of Renin, 4 out of 7 had hypertension, NOMID patients did not have hypertension. Treatment with anakinra and baricitinib normalized 143 and 142 of dysregulated proteins in NOMID and CANDLE respectively.Conclusion:Differentially expressed proteins in NOMID and CANDLE are consistent with innate immune cell activation. Distinct endothelial cell signatures in NOMID and CANDLE may provide mechanistic insight into differences in vascular phenotypes. Treatment with anakinra and Baricitinib in NOMID and CANDLE leaves 30% and 13% of the dysregulated proteins unchanged.Acknowledgments:This work was supported by Intramural Research atNational Institute of Allergy Immunology and Infectious Diseases of National Institutes of Health, Bethesda, Maryland, the Center of Human Immunology and was approved by the IRB.Disclosure of Interests:None declared

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Circulating miRNAs Related to Epithelial–Mesenchymal Transitions (EMT) as the New Molecular Markers in Endometriosis

Current Issues in Molecular Biology ◽

10.3390/cimb43020064 ◽

2021 ◽

Vol 43 (2) ◽

pp. 900-916

Author(s):

Anna Zubrzycka ◽

Monika Migdalska-Sęk ◽

Sławomir Jędrzejczyk ◽

Ewa Brzeziańska-Lasota

Keyword(s):

Molecular Mechanisms ◽

Immune Cell ◽

Epithelial Mesenchymal Transition ◽

Clinical Symptoms ◽

Diagnostic Tools ◽

Endometrial Stromal Cells ◽

Disease Etiology ◽

Diagnostic Biomarkers ◽

Mesenchymal Transition ◽

Non Invasive

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial–mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.

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Decision making under ambiguity and risk in adolescent-onset schizophrenia

BMC Psychiatry ◽

10.1186/s12888-021-03230-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dandan Li ◽

Fengyan Zhang ◽

Lu Wang ◽

Yifan Zhang ◽

Tingting Yang ◽

...

Keyword(s):

Decision Making ◽

Executive Function ◽

Iowa Gambling Task ◽

Clinical Symptoms ◽

Healthy Controls ◽

Syndrome Scale ◽

Significant Difference ◽

Abnormal Pattern ◽

Negative Syndrome ◽

The Relationship

Abstract Objective Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia. Methods We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson’s correlation revealed the relationship among total score of DM and clinical and neuropsychological data. Results Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study. Conclusions Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.

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370 Pure Primary Small Cell Carcinoma of the Prostate: A Rare Entity

British Journal of Surgery ◽

10.1093/bjs/znab134.549 ◽

2021 ◽

Vol 108 (Supplement_2) ◽

Author(s):

C Desai ◽

A Bhojwani ◽

J Parkin

Keyword(s):

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Clinical Symptoms ◽

Positive Family History ◽

Malignant Neoplasm ◽

Small Cell ◽

Whole Body ◽

Carcinoma Of The Prostate ◽

Patient Reported ◽

Prostate Cancers

Abstract Introduction We report a case of small cell carcinoma of the prostate (SCCP) which is a rare, high-grade malignant neoplasm accounting for 1% of all prostate cancers (CPa). Case Presentation A 56-year-old male patient initially presented to primary care with a six-month history of frequency, nocturia and pain in the perineal region when seated. A positive family-history for CPa was noted, serum PSA was 11.58, and a rectal examination found a large, irregular mass. He was treated with antibiotics for possible prostatitis and referred to the colorectal team. MRI rectum confirmed a mass between the prostate and rectum, which was found to be pure SCCP on biopsy. Whole-body scanning found multiple lung and pelvic metastases. The patient was commenced on six cycles of Etoposide and Carboplatin therapy. The patient reported that his pelvic discomfort has improved following the first cycle. Conclusions SCCP metastasizes early and therefore the clinical presentation is often in an advanced stage. It is noted that there is limited value of serum PSA for SCCP diagnosis. Instead, pathological examinations and MRI rectum are vital. In terms of treatment, chemotherapy provides relief of the clinical symptoms and its use is in in accordance with the 2016 National Comprehensive Cancer Network guidelines.

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Association between HOX Transcript Antisense RNA Single-Nucleotide Variants and Recurrent Implantation Failure

International Journal of Molecular Sciences ◽

10.3390/ijms22063021 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3021

Author(s):

Jeong Yong Lee ◽

Eun Hee Ahn ◽

Hyeon Woo Park ◽

Ji Hyang Kim ◽

Young Ran Kim ◽

...

Keyword(s):

Antisense Rna ◽

Coagulation Factors ◽

Healthy Controls ◽

Implantation Failure ◽

Single Nucleotide Variants ◽

Recurrent Implantation Failure ◽

Single Nucleotide ◽

Vitro Fertilization ◽

And Control

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization–embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.

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