scholarly journals Single Nucleotide Polymorphisms in PPARD Associated with Systemic Lupus Erythematosus in Chinese Populations

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yuan-yuan Qi ◽  
Ya-ling Zhai ◽  
Xin-ran Liu ◽  
Xiao-xue Zhang ◽  
Ya-fei Zhao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Genetic Association ◽  
Lupus Erythematosus ◽  
Organ Damage ◽  
Clinical Analysis ◽  
Multiple Organ ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus ◽  
Chinese Populations ◽  
Biological Studies

Background. Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by apoptotic clearance deficiency provoking autoimmune responses and leading to multiple organ damage. PPAR-δ, encoded by the PPARD gene, was induced in macrophages promoting the timely disposal of apoptotic cells. Biological studies had provided solid foundation of PPARD involvement in SLE; it is worthwhile to further explore the genetic contribution of PPARD to SLE. Methods. We performed a discovery-replication genetic association study. The discovery study was based on previous reported GWAS data. And the replication study was conducted in 1003 SLE patients and 815 healthy controls from Henan, Middle East of China. Further, we analyzed the eQTL effect to identify possible functional significance. Results. In the genetic association analysis, we observed significant association between the risk C allele of rs4713853 (p=0.03, OR 1.167, 95% CI 1.015-1.341) and increased SLE susceptibility. Moreover, individuals with the risk C allele were associated with lower expression of PPARD and DEF6. Our clinical analysis showed that SLE patients with the risk C allele of rs4713853 were more likely to present a higher proportion of anti-Sm antibody presence (CC+CT vs. TT, 20.0% vs. 14.2%, p=0.039) and higher level of Scr (median inter quarter range CC+CT vs. TT, 56 48-71 vs. 54 46-64 μmol/L, p=0.002). Conclusions. In conclusion, our study identified a novel association between PPARD rs4713853 and SLE susceptibility in Chinese populations. By integrating multiple layers of analysis, we suggested that PPARD might be a main candidate in the pathogenesis of SLE.

scholarly journals Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yuan-yuan Qi ◽  
Xin-ran Liu ◽  
Ying-xin He ◽  
Min Zhou ◽  
Xiang-hui Ning ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Genetic Association ◽  
Lupus Erythematosus ◽  
Genome Wide Association Study ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Chinese Populations ◽  
Genetic Heritability

A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of telomere. Given that only a small portion of the genetic heritability of SLE has been explained so far, we aimed to identify novel loci in telomere-related genes responsible for SLE susceptibility in Chinese populations. We performed a comprehensive genetic association analysis of SLE with telomere-related genes. To identify functional significance, we analyzed the publicly available HaploReg v4.1 and RegulomeDB databases. Differential gene expression analysis was also performed using ArrayExpress. A novel signal of PINX1 rs6984094 was identified ( P discovery = 4.13 × 10 − 2 , OR = 0.58 , 95% CI 0.35-0.98) and successfully replicated ( P replication = 5.73 × 10 − 3 , OR = 0.45 , 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the PINX1 rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of PINX1 mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between PINX1 (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations.

scholarly journals Cytokine Networks in Systemic Lupus Erythematosus

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Hooi-Ming Lee ◽  
Hidehiko Sugino ◽  
Norihiro Nishimoto
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Cytokine Production ◽  
Organ Damage ◽  
Multiple Organ ◽  
Serum Cytokine ◽  
Systemic Lupus ◽  
Pathological Conditions ◽  
Cytokine Levels ◽  
Cytokine Networks

Systemic lupus erythematosus (SLE) is an autoimmune disease more prominent in women and characterized by multiple organ damage. Imbalance in cytokine production and cytokine levels correlates with SLE progression, making the understanding of SLE cytokine networks very important for SLE treatment strategy and drug development. In this article, we review cytokine networks that may be involved in the pathogenesis of SLE by briefly describing abnormal cytokine production and serum cytokine levels in SLE patients. We also focus on the pathological roles of cytokines and their interactions in immunoregulatory networks and suggest how their disturbances may implicate in pathological conditions in SLE. Finally, we further discuss the influence of estrogen on these cytokine networks.

Cognitive and Psychiatric Manifestations of Childhood-Onset Systemic Lupus Erythematosus

2010 ◽  
Author(s):  
Deborah M. Levy ◽  
Gail S. Ross
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Organ Damage ◽  
Multiple Organ ◽  
Childhood Onset ◽  
Systemic Lupus ◽  
Disease Manifestation ◽  
American College Of Rheumatology ◽  
Organ Systems ◽  
Similar Disease

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against multiple organ systems. Individuals with SLE may have disease of only one organ system or of many organ systems at one time during a “flare” of disease activity. Systemic lupus erythematosus is characterized by multiple flares and remissions, and flares may lead to end-organ damage. The diagnosis of SLE is generally made by fulfilling four out of 11 of the American College of Rheumatology (ACR) 1997 Revised Classification Criteria for SLE (Hochberg 1997). Although the 1997 revised criteria have not been validated, the earlier 1982 criteria (Tan et al. 1982) have a sensitivity of 96% and specificity of 100%in childhood-onsetSLE(cSLE) (Ferraz et al. 1994). See Table 3.1 for these criteria. Systemic lupus erythematosus has a prevalence rate of 500 per million persons in the U.S. population (Klippel 1997) but may be as high as 130 per 100,000 persons (Uramoto et al. 1999). Approximately 15% of all SLE has its onset in childhood (prior to 18 years of age). Systemic lupus erythematosus occurs more commonly in non-Caucasians, with greater severity of SLE in children and adult Latino and African Americans than in non-Latino Caucasians (Michet et al. 1979).The female predominance of SLE in adulthood (10:1 female-to-male ratio) is less pronounced in childhood, and the ratio prior to puberty is more likely to be 5:1 or even 3:1.The majority of cSLE cases have onset in the peripubertal age period (10–15 years), which continues to suggest a link between estrogen and other hormones on the development of SLE. Childhood-onset SLE differs from adult-onset SLE in that the frequency of renal disease is higher, and the incidence and prevalence of neuropsychiatric SLE (NPSLE) is probably greater (Tucker et al. 1995; Sibbit et al. 2002). Children require aggressive immunosuppression, which on a dose per kilogram of body weight is generally higher than that required by an adult to treat a similar disease manifestation. Immunosuppression often includes corticosteroids. At least in adults, corticosteroids do not appear to cause cognitive impairment (Carbette et al. 1986; Denburg et al. 1997; Carlomagno et al. 2000).

scholarly journals Transancestral mapping of the MHC region in systemic lupus erythematosus identifies new independent and interacting loci at MSH5, HLA-DPB1 and HLA-G

2012 ◽  
Vol 71 (5) ◽  
pp. 777-784 ◽  
Author(s):  
Michelle M A Fernando ◽  
Jan Freudenberg ◽  
Annette Lee ◽  
David Lester Morris ◽  
Lora Boteva ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Association Studies ◽  
Organ Damage ◽  
Genome Wide Association Studies ◽  
Systemic Lupus ◽  
Chinese Populations ◽  
Risk Alleles ◽  
Snp Mapping ◽  
Hla Dqa1

ObjectivesSystemic lupus erythematosus (SLE) is a chronic multisystem genetically complex autoimmune disease characterised by the production of autoantibodies to nuclear and cellular antigens, tissue inflammation and organ damage. Genome-wide association studies have shown that variants within the major histocompatibility complex (MHC) region on chromosome 6 confer the greatest genetic risk for SLE in European and Chinese populations. However, the causal variants remain elusive due to tight linkage disequilibrium across disease-associated MHC haplotypes, the highly polymorphic nature of many MHC genes and the heterogeneity of the SLE phenotype.MethodsA high-density case-control single nucleotide polymorphism (SNP) study of the MHC region was undertaken in SLE cohorts of Spanish and Filipino ancestry using a custom Illumina chip in order to fine-map association signals in these haplotypically diverse populations. In addition, comparative analyses were performed between these two datasets and a northern European UK SLE cohort. A total of 1433 cases and 1458 matched controls were examined.ResultsUsing this transancestral SNP mapping approach, novel independent loci were identified within the MHC region in UK, Spanish and Filipino patients with SLE with some evidence of interaction. These loci include HLA-DPB1, HLA-G and MSH5 which are independent of each other and HLA-DRB1 alleles. Furthermore, the established SLE-associated HLA-DRB1*15 signal was refined to an interval encompassing HLA-DRB1 and HLA-DQA1. Increased frequencies of MHC region risk alleles and haplotypes were found in the Filipino population compared with Europeans, suggesting that the greater disease burden in non-European SLE may be due in part to this phenomenon.ConclusionThese data highlight the usefulness of mapping disease susceptibility loci using a transancestral approach, particularly in a region as complex as the MHC, and offer a springboard for further fine-mapping, resequencing and transcriptomic analysis.

scholarly journals Oral lesions as a clinical sign of systemic lupus erythematosus

2018 ◽  
Vol 51 (3) ◽  
pp. 147
Author(s):  
Eliza Kristina M. Munthe ◽  
Irna Sufiawati
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Organ Damage ◽  
Multiple Organ ◽  
Suspected Case ◽  
Oral Lesions ◽  
Systemic Lupus ◽  
Organ Systems ◽  
High Degree

Background: Oral lesions represent one of the most important clinical symptoms of systemic lupus erythematosus (SLE), an autoimmune disease with a high degree of clinical variability rendering it difficult to arrive at a prompt and accurate diagnosis. There are many unknown causes and multiple organ systems involved, with the result that permanent organ damage may occur before treatment commences. Purpose: The purpose of this case report is to discuss the importance of recognizing the lesions related to SLE which may help dentists to make an early diagnosis. Case: A 17-year-old female patient was referred by the Internal Medicine Department with a suspected case of SLE. Prior to admittance to the hospital, the patient was diagnosed with tuberculosis. A subsequent extraoral examination revealed ulceration with a blackish crust on the upper lip. An intraoral examination showed similar ulceration covered with a blackish crust on the labial mucosa accompanied by central erythema in the hard palate. Blood tests indicated decreased levels of hemoglobin, hematocrit and platelets, but increased levels of leukocytes. A diagnosis of oral lesions associated with SLE and angioedema was formulated. Case management: The patient was given 1% hydrocortisone and vaseline album for extraoral lesions, while 0.2% chlorhexidine gluconate and 0.1% triamcinolone acetonide was used to treat intraoral lesions. An improvement in the oral lesions manifested itself after two weeks of treatment. Conclusion: Early detection of oral lesions plays a significant role in diagnosing SLE. It is important for the dentist to recognize the presentation of diseases that may be preceded by oral lesions. A multidisciplinary approach and appropriate referrals are necessary to ensure comprehensive medical and dental management of patients with SLE.

scholarly journals Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus

2007 ◽  
Vol 67 (4) ◽  
pp. 458-461 ◽  
Author(s):  
A H Sawalha ◽  
K M Kaufman ◽  
J A Kelly ◽  
A J Adler ◽  
T Aberle ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Genetic Association ◽  
Lupus Erythematosus ◽  
Plasma Cells ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
B Cell Differentiation ◽  
Systemic Lupus ◽  
Association Analyses ◽  
Risk Alleles

Objective:The aetiology of systemic lupus erythematosus (SLE) is incompletely understood. Both genetic and environmental factors are implicated in the pathogenesis of the disease. Herein, we describe genetic association between SLE and polymorphisms in the interleukin (IL)-21 gene. The reported effect of IL-21 on B-cell differentiation into plasma cells and its effect on dendritic cell maturation and T-cell responses make IL-21 an attractive candidate gene for SLE.Methods:Three single nucleotide polymorphisms (SNPs) in the IL-21 gene were genotyped in a total of 2636 individuals (1318 cases and 1318 controls matched for age, sex and race). Population-based case–control association analyses were performed.Results:We found a genetic association with SLE and two SNPs located within the IL-21 gene (rs907715: χ2 = 11.55, p<0.001; rs2221903: χ2 = 5.49, p = 0.019). Furthermore, genotypes homozygous for the risk alleles were more frequent than genotypes homozygous for the non-risk alleles in European–American patients as compared to controls (rs907715 (GG versus AA): odds ratio (OR) = 1.66, p = 0.0049; rs2221903 (GG versus AA): OR = 1.60, p = 0.025).Conclusion:Our findings indicate that IL-21 polymorphism is a candidate association with SLE. The functional effects of this association, when revealed, might improve our understanding of the disease and provide new therapeutic targets.

scholarly journals Association of Melatonin Pathway Gene’s Single-Nucleotide Polymorphisms with Systemic Lupus Erythematosus in a Chinese Population

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Peng Wang ◽  
Lei Liu ◽  
Li-Fang Zhao ◽  
Chan-Na Zhao ◽  
Yan-Mei Mao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Association ◽  
Lupus Erythematosus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Significant Difference

Objectives. This study was to investigate the association of melatonin (MTN) pathway gene’s single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE). Methods. We recruited 495 SLE patients and 493 healthy controls, 11 tag SNPs in MTN receptor 1a (MTNR1a), MTNR1b, and arylalkylamine N-acetyltransferase (AANAT) genes were genotyped and analyzed. Serum MTN concentration was determined by enzyme-linked immunosorbent assay (ELISA) kits. Results. Two SNPs of AANAT gene (rs8150 and rs3760138) associated with the risk of SLE; CC carriers of rs8150 had a lower risk as compared to GG (OR=0.537, 95% CI: 0.361, 0.799), whereas GG carrier in rs3760138 had an increased risk (OR=1.823, 95% CI: 1.154, 2.880) compared to TT. However, we did not find any genetic association between the other nine SNPs with SLE risk. Case-only analysis showed associations of rs2165667 and rs1562444 with arthritis, rs10830962 with malar rash, rs3760138 with immunological abnormality, and rs8150 with hematological abnormality. Furthermore, a significant difference between plasma MTN levels with different genotypes of rs1562444 was observed. Haplotype analyses revealed that haplotype of CCTAT, CTAGT, and GGG was significantly associated with the increased risk in SLE susceptibility, but TCTAT and CTG appeared to be a protective haplotype. Conclusions. The present study supported the genetic association of MTN pathway genes with SLE susceptibility and specific clinical manifestations, suggesting the potential role of MTN pathway genes in the pathogenesis and development of SLE.

scholarly journals SCUBE3 Is Likely a Susceptibility Gene for Systemic Lupus Erythematosus for Chinese Populations

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yuan-yuan Qi ◽  
Ya-fei Zhao ◽  
Ya-ling Zhai ◽  
Xiao-xue Zhang ◽  
Xiao-yang Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mrna Expression ◽  
Lupus Erythematosus ◽  
Susceptibility Gene ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus ◽  
Single Nucleotide ◽  
Chinese Populations ◽  
Genetic Susceptibility Factor

Background. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic disposition with more than 100 susceptibility genes identified until now. However, our knowledge on SLE genetic background is still limited. The present study was aimed at evaluating the role of single nucleotide polymorphisms (SNPs) in SCUBE3, a TGF-β signaling activator, with SLE susceptibility in Chinese populations. Methods. A total of 2801 individuals (490 cases and 493 controls from GWAS cohort and 1003 cases and 815 controls from our cohort) were enrolled, and SNPs located 10 kb up- and downstream of SCUBE3 (chr6:35182190-35218609) were included in the genetic association study. Multiple layers of bioinformatics were conducted, and the levels of SCUBE3 expression were confirmed. Results. Of the 31 SNPs in SCUBE3 tested, 24 SNPs were significantly associated with SLE at p ≤ 0.05 . The top locus was rs1888822 with p = 8.74 ∗ 10 − 6 in the discovery cohort and was confirmed by the replication cohort with p = 0.012 . Additionally, the levels of SCUBE3 mRNA expression were significantly lower in patients with SLE comparing with healthy controls ( p = 4.28 ∗ 10 − 4 ). Further expression data from ArrayExpress showed that the expression of SCUBE3 was also lower in CD3+ T cells and B cells from patients with SLE. Conclusions. Our research revealed that variants in SCUBE3, which encode SCUBE3 as a TGF-β signaling activator, can be considered as a new genetic susceptibility factor for systemic lupus erythematosus. And the reduced mRNA expression of SCUBE3 was first reported in patients with SLE.

scholarly journals Research Progress on Regulatory B Cells in Systemic Lupus Erythematosus

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Tao Wang ◽  
Yongjun Mei ◽  
Zhijun Li
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Transforming Growth Factor ◽  
Organ Damage ◽  
Multiple Organ ◽  
Research Progress ◽  
Regulatory B Cells ◽  
Systemic Lupus ◽  
B Cell Subsets

Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune inflammatory disease characterized by the production of numerous autoantibodies and cytokines, as well as multiple organ damage. Specific B cell subsets negatively regulate immune responses and have been termed regulatory B cells (Bregs). Bregs are characterized by the production of the immunoregulatory cytokines interleukin (IL)-10, IL-35, and transforming growth factor (TGF)-β. Bregs suppress other immune cells through the secretion of these immunosuppressive cytokines and have thus been studied extensively for their potential role in the treatment of various autoimmune diseases. The progress of the research on Bregs and SLE in recent years is reviewed in this paper.

scholarly journals The ZNF76 rs10947540 polymorphism associated with systemic lupus erythematosus risk in Chinese populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuan-yuan Qi ◽  
Yan Cui ◽  
Hui Lang ◽  
Ya-ling Zhai ◽  
Xiao-xue Zhang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Zinc Finger Protein ◽  
Meta Analysis ◽  
Bioinformatic Analysis ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus ◽  
Chinese Han ◽  
Chinese Populations ◽  
Stratified Analysis

AbstractSystemic lupus erythematosus (SLE) is a typical autoimmune disease with a strong genetic disposition. Genetic studies have revealed that single-nucleotide polymorphisms (SNPs) in zinc finger protein (ZNF)-coding genes are associated with susceptibility to autoimmune diseases, including SLE. The objective of the current study was to evaluate the correlation between ZNF76 gene polymorphisms and SLE risk in Chinese populations. A total of 2801 individuals (1493 cases and 1308 controls) of Chinese Han origin were included in this two-stage genetic association study. The expression of ZNF76 was evaluated, and integrated bioinformatic analysis was also conducted. The results showed that 28 SNPs were associated with SLE susceptibility in the GWAS cohort, and the association of rs10947540 was successfully replicated in the independent replication cohort (Preplication = 1.60 × 10−2, OR 1.19, 95% CI 1.03–1.37). After meta-analysis, the association between rs10947540 and SLE was pronounced (Pmeta = 9.62 × 10−6, OR 1.29, 95% CI 1.15–1.44). Stratified analysis suggested that ZNF76 rs10947540 C carriers were more likely to develop relatively high levels of serum creatinine (Scr) than noncarriers (CC + CT vs. TT, p = 9.94 × 10−4). The bioinformatic analysis revealed that ZNF76 rs10947540 was annotated as an eQTL and that rs10947540 was correlated with decreased expression of ZNF76. Remarkably, significantly reduced expression of ZNF76 was confirmed by expression data from both our laboratory and an array-based expression database. Taken together, these results suggest that ZNF76 rs10947540 is a possible susceptibility factor associated with SLE susceptibility. The mechanism underlying the relationship between ZNF76 and SLE pathogenesis still requires further investigation.

Sign in / Sign up

Export Citation Format

Share Document