Association of NLRP3 rs35829419 and rs10754558 Polymorphisms With Risks of Autoimmune Diseases: A Systematic Review and Meta-Analysis

The existing knowledge about the association between NLRP3 rs35829419/rs10754558 polymorphisms and susceptibility to autoimmune diseases (AIDs) remains controversial. Herein, a meta-analysis was performed to evaluate such association. We searched databases for relevant studies published in English up to February 2021. Stata14 was used to assess the odds ratio (OR). As for NLRP3 rs35829419, no significant association to overall AIDs was found in three genetic models [A vs. C: OR (95%CI) = 0.89 (0.69–1.14); AC vs. CC: 1.00 (0.77–1.30); AA/AC vs. CC: 0.93 (0.71–1.20)]. However, subgroup analysis by disease type showed that NLRP3 rs35829419 A allele may have a significant protective effect on rheumatoid arthritis (RA) susceptibility [A vs. C: 0.74 (0.57–0.96)]. NLRP3 rs10754558 polymorphism contributes to significantly reduce the risk of AIDs in the allelic model [G vs. C: 0.78 (0.71–0.87)], homozygote co-dominant model [GG vs. CC: 0.63 (0.51–0.77)], heterozygote co-dominant model [GC vs. CC: 0.78 (0.66–0.91)], dominant model [GG/GC vs. CC: 0.73 (0.63–0.84)], and recessive model [GG vs. GC/CC: 0.73 (0.62–0.88)]. In the subgroup analysis by ethnicity, association was observed between the NLRP3 rs10754558 G allele and AIDs in Latin Americans, but not in European, Arabian, or Asian populations. Stratification by disease type showed a significant association of the NLRP3 rs10754558 G allele with type 1 diabetes (T1D), RA, and systemic lupus erythematosus (SLE), but not with celiac disease (CD), multiple sclerosis (MS), or myasthenia gravis (MG). This meta-analysis suggests that the NLRP3 rs10754558, but not rs35829419, polymorphism is associated with susceptibility to AIDs, especially in Latin American individuals.

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Association between functional NLRP3 polymorphisms and susceptibility to autoimmune and inflammatory diseases: a meta-analysis

Lupus ◽

10.1177/0961203316644336 ◽

2016 ◽

Vol 25 (14) ◽

pp. 1558-1566 ◽

Cited By ~ 8

Author(s):

Y H Lee ◽

S-C Bae

Keyword(s):

Celiac Disease ◽

Latin American ◽

Comparative Studies ◽

Inflammatory Diseases ◽

Meta Analysis ◽

Recessive Model ◽

Disease Type ◽

Asian Populations ◽

Autoimmune And Inflammatory Diseases ◽

Allele Contrast

Objective This study determined whether NLRP3 polymorphisms rs35829419 C/A and rs10754558 C/G were associated with autoimmune and inflammatory diseases. Methods An association between the NLRP3 rs35829419 C/A and rs10754558 C/G polymorphisms and autoimmune and inflammatory diseases was determined by performing a meta-analysis by using (1) allele contrast, (2) recessive, (3) dominant, and (4) co-dominant models. Results Thirty comparative studies involving 8069 patients and 8824 controls were included in the meta-analysis. No association was observed between autoimmune and inflammatory diseases and NLRP3 rs35829419 C allele (OR = 1.020, 95% CI = 0.804–1.295, p = 0.869). Stratification by ethnicity showed no association between the NLRP3 rs35829419 C allele and autoimmune and inflammatory diseases in European, Latin American, and Polynesian populations. Stratification by disease type showed no association between the NLRP3 rs35829419 C allele and gout, SLE, RA, celiac disease, and Crohn’s disease. Moreover, no association was observed between autoimmune and inflammatory diseases and the NLRP3 rs10754558 C allele (OR = 1.057, 95% CI = 0.950–1.177, p = 0.310). However, stratification by ethnicity showed an association between the NLRP3 rs10754558 C allele and autoimmune and inflammatory diseases in the Latin American (OR = 1.399, 95% CI = 1.201–1.630, p = 1.6 × 10–6) but not in European and Asian populations. Further, stratification by disease type showed a significant association of the NLRP3 rs10754558 C allele with SLE (OR = 1.465 95% CI = 1.144–1.875, p = 0.002) but not with gout and celiac disease. The same pattern was observed for the NLRP3 rs10754558 C allele in the recessive model. Conclusions Our results indicated that the NLRP3 rs10754558 C/G polymorphism was associated with susceptibility to SLE and with autoimmune and inflammatory diseases in Latin American individuals.

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Association between BRCA1 polymorphisms rs799917 and rs1799966 and breast cancer risk: a meta-analysis

Journal of International Medical Research ◽

10.1177/0300060519826819 ◽

2019 ◽

Vol 47 (4) ◽

pp. 1409-1416

Author(s):

Meiming Yang ◽

Xiaoli Du ◽

Feng Zhang ◽

Shifang Yuan

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Confidence Intervals ◽

Subgroup Analysis ◽

Meta Analysis ◽

Recessive Model ◽

Dominant Model ◽

Odds Ratios

Background Several studies have reported correlations between BRCA1 polymorphisms rs799917 and rs1799966 with the risk of breast cancer (BC). However, this relationship remains controversial. Methods We conducted a meta-analysis of seven studies to assess the associations between BRCA1 rs799917 and rs1799966 and BC risk, with the aim of more accurately determining the potential correlation. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the correlation of rs799917 and rs1799966 with BC risk. Results There was no overall correlation between BRCA1 rs799917 and BC risk (TT vs CC: OR = 0.87, 95% CI = 0.66–1.16; CT vs CC: OR = 1.02, 95% CI = 0.89–1.15; dominant model: OR = 0.99, 95% CI = 0.88–1.11; recessive model: OR = 0.87, 95% CI = 0.65–1.16). Subgroup analysis by ethnicity also revealed no significant correlation between rs799917 and BC risk in either Asians or Caucasians. There was also no significant association between BRCA1 rs1799966 and BC risk (GG vs AA: OR = 0.70, 95% CI = 0.33–1.47; AG vs AA: OR = 0.68, 95% CI = 0.35–1.30; dominant model: OR = 0.76, 95% CI = 0.49–1.06; recessive model: OR = 0.82, 95% CI = 0.49–1.36). Conclusion BRCA1polymorphisms rs799917 and rs1799966 were not significantly associated with BC risk in this meta-analysis.

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Interleukin 4 gene polymorphism (−589C/T) and the risk of asthma: a meta-analysis and met-regression based on 55 studies

BMC Immunology ◽

10.1186/s12865-020-00384-7 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Ahmad Kousha ◽

Armita Mahdavi Gorabi ◽

Mehdi Forouzesh ◽

Mojgan Hosseini ◽

Markov Alexander ◽

...

Keyword(s):

Asian American ◽

Subgroup Analysis ◽

Literature Search ◽

Meta Analysis ◽

East Asian ◽

Recessive Model ◽

Interleukin 4 ◽

Case Control Studies ◽

Asian Populations ◽

Allelic Model

Abstract Background Numerous investigations have previously evaluated the association of interleukin (IL) 4 gene polymorphisms and the risk of asthma, conferring inconsistent results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of IL4 gene −589C/T (rs2243250) polymorphism and susceptibility to asthma. Methods A systematic literature search was performed in ISI web of science, Scopus, Medline/PubMed databases prior to September 2020, and the pooled odds ratio (OR) and their corresponding 95% CI were calculated to determine the association strength. Results Literature search led to retrieving of 49 publications (55 case-control studies) containing 9572 cases and 9881 controls. It was revealed that IL4 gene −589C/T polymorphism increased the risk of asthma across all genetic models, including dominant model (OR = 1.22), recessive model (OR = 1.17), allelic model (OR = 1.21), and TT vs. CC model (OR = 1.34), but not the CT vs. TT model. The subgroup analysis by age indicated that IL4 gene -589C/T polymorphism was significantly associated with asthma risk in both pediatrics and adults. Additionally, the subgroup analysis by ethnicity revealed significant association in Asian, American, and Europeans. Finally, subgroup analysis by East Asian and non-East Asian populations indicated significant associations. Conclusions The current meta-analysis revealed that IL4 gene -589C/T polymorphism was a susceptibility risk in both pediatrics and adults in the whole and different ethnic groups.

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Association of the rs17250932, rs4794067 and rs2240017 polymorphism in the TBX21 gene with autoimmune diseases

Allergologia et Immunopathologia ◽

10.15586/aei.v49i3.80 ◽

2021 ◽

Vol 49 (3) ◽

pp. 83-90

Author(s):

Haili Wang ◽

Hong Wang ◽

Yue Wu ◽

Hua-yun Ling ◽

Ling-ling Wu ◽

...

Keyword(s):

Autoimmune Diseases ◽

Publication Bias ◽

Meta Analysis ◽

Biomedical Literature ◽

Dominant Model ◽

Contrast Model ◽

Pooled Data ◽

Asian Populations ◽

Tbx21 Gene ◽

Model Publication

Objective: To evaluate systematically the association between TBX21 gene polymorphisms (rs17250932, rs2240017, and rs4794067) and the risk of autoimmune diseases in Asian populations. Methods: The Medline, Web of Science, and Chinese Biomedical Literature Database were used to retrieve eligible studies that were published before July 2020. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by using the dominant model, heterozygote contrast model, and allelic contrast model. Publication bias was evaluated using contour-enhanced funnel plots and Egger’s regression test. Sensitivity analysis was conducted to assess the robustness of this meta-analysis.Results: A total of 12 eligible studies, including 3834 patients and 4824 healthy controls, were recruited in this meta-analysis. The pooled data demonstrated that TBX21 rs2240017 and rs4794067 polymorphisms were significantly associated with the risk of autoimmune diseases in Asian populations in allelic contrast model (OR: 1.456, 95% CI: 1.131–1.875, P = 0.004; OR: 0.766, 95% CI: 0.615–0.954, P = 0.017), heterozygote comparison model (OR: 1.647, 95% CI: 1.239–2.189, P = 0.001; OR: 0.796, 95% CI: 0.634–0.999, P = 0.049), and dominant model (OR: 1.572, 95% CI: 1.194–2.071, P = 0.004; OR: 0.767, 95% CI: 0.607–0.970, P = 0.027). The G allele of rs2240017 may be a risk factor for autoimmune diseases, and the T allele of rs4794067 may increase the risk of autoimmune diseases. However, we failed to find evidence of the association between TBX21 rs17250932 polymorphism and susceptibility to autoimmune diseases. No publication bias was established in this meta-analysis.Conclusion: This meta-analysis indicated that TBX21 rs2240017 and rs4794067 polymorphism confer susceptibility to autoimmune diseases, but not rs17250932.

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Association of TNFSF4 rs1234315, rs2205960 polymorphisms and systemic lupus erythematosus susceptibility: a meta-analysis

Lupus ◽

10.1177/0961203319862610 ◽

2019 ◽

Vol 28 (10) ◽

pp. 1197-1204

Author(s):

J -M Wang ◽

Z -C Yuan ◽

A -F Huang ◽

W -D Xu

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Tumor Necrosis ◽

Meta Analysis ◽

Additive Model ◽

Recessive Model ◽

Dominant Model ◽

Systemic Lupus ◽

Systemic Lupus Erythematosus Susceptibility ◽

Necrosis Factor

Background The aim of this study was to explore the association between tumor necrosis factor superfamily number 4 (TNFSF4) rs1234315, rs2205960 polymorphisms and systemic lupus erythematosus (SLE) susceptibility. Methods A meta-analysis was performed on the association between rs1234315 and rs2205960 polymorphisms and SLE by allelic contrast, additive model, recessive model and dominant model. Results Regarding rs1234315 polymorphism, a total of five studies were included (6575 cases, 14,798 controls). Meta-analysis showed significant associations between the T allele and SLE in overall subjects and Asians (OR = 1.310, 95%CI: 1.104–1.553, p = 0.002; OR = 1.458, 95%CI: 1.328–1.602, p < 0.001). With respect to the rs2205960 polymorphism, significant associations between the T allele and SLE were found in all subjects (OR = 1.333, 95%CI: 1.254–1.418, p < 0.001), Asians (OR = 1.407, 95%CI: 1.345–1.471, p < 0.001) and Europeans (OR = 1.254, 95%CI: 1.185–1.328, p < 0.001). Results also showed significant associations between the additive model and SLE in all subjects and Asians (OR = 1.934, 95%CI: 1.500–2.494, p < 0.001; OR = 1.882, 95%CI: 1.318–2.689, p = 0.001). Furthermore, we detected significant associations between the dominant model and SLE in all subjects and Asians (OR = 1.421, 95%CI: 1.239–1.629, p < 0.001; OR = 1.297, 95%CI: 1.083–1.555, p = 0.005). Significant associations were found between the recessive model and SLE in overall subjects and Asians (OR = 1.677, 95%CI: 1.312–2.144, p < 0.001; OR = 1.751, 95%CI: 1.235–2.483, p = 0.002). Conclusion The present study suggested that TNFSF4 rs1234315 and rs2205960 polymorphisms were associated with SLE susceptibility.

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PREDICTION AND ANALYSIS OF VACCINATION POSSIBILITIES IN AUTOIMMUNE DISEASES: AN APPLICATION OF ARTIFICIAL IMMUNE SYSTEM

Journal of Biological System ◽

10.1142/s0218339002000536 ◽

2002 ◽

Vol 10 (02) ◽

pp. 107-126

Author(s):

RAJANI R. JOSHI ◽

BHUVANESWARAN NATARAJAN

Keyword(s):

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Artificial Immune System ◽

Real Data ◽

Affinity Maturation ◽

Artificial Immune ◽

Humoral Immune ◽

Machine Learning Model ◽

Experimental Findings

We present an adaptive machine learning model of the humoral immune response. Antigens (epitopes/ids) and antibodies (paratopes/anti-ids) are represented here as sequences of single letter amino acid codes. The model effectively simulates dynamic affinity maturation, memory and associativity. Specific age-function is derived here based on recent experimental findings and is used to incorporate self and non-self antigens. Computational experiments using real data on Type-1 Diabetes and Systemic Lupus Erythematosus offer quantitative elucidation of autoimmunity. The results also provide applications towards vaccine design and possible solution to the therapeutic difficulties in the autoimmune diseases and disorders of the above kind.

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FokI polymorphism of the vitamin D receptor (VDR) gene and susceptibility to tuberculosis: evidence through a meta-analysis

10.21203/rs.3.rs-266491/v1 ◽

2021 ◽

Author(s):

Upendra Yadav ◽

Pradeep Kumar ◽

Vandana Rai

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Meta Analysis ◽

Receptor Gene ◽

Asian Population ◽

Recessive Model ◽

Dominant Model ◽

Vdr Gene ◽

Exact Relation ◽

Significance Level

Abstract Background: Tuberculosis is one of the top ten causes of deaths worldwide. The deficiency of vitamin D was reported to be associated with the increased susceptibility of tuberculosis. Various previous reports were published to check the association of FokI polymorphism of the vitamin D receptor gene with tuberculosis risk. But their results were inconsistent so, we performed a meta-analysis to know the exact relation of the two.Methods: Different databases were screened up to November, 2020 with the keywords “Vitamin D receptor”, “VDR”, and “FokI”, along with “Tuberculosis” and “TB” to find the suitable articles. All the statistical analyses were performed by the Open Meta-Analyst program and all p-values were two-tailed with a significance level of 0.05.Results: No statistically significant association was observed in the allele contrast model (ORfvs.F= 1.11, 95%CI= 0.99-1.24, p= 0.05, I2= 73.46%), in the dominant model (ORff+Ffvs.FF= 1.11, 95%CI= 0.96-1.28, p= 0.14, I2= 71.39%), and in the co-dominant model (ORFfvs.FF= 1.05, 95%CI= 0.92-1.21, p= 0.41, I2= 65.97%). However, a significant association was found in the homozygote model (ORffvs.FF= 1.32, 95%CI= 1.03-1.69, p= 0.02, I2= 67.02%) and in the recessive model (ORFF+Ff vs.ff= 1.26, 95%CI= 1.03-1.54, p= 0.02, I2= 58.01%). Further analysis was performed on the bases of the ethnicity. In Asian population a significant association was found in the homozygote model (ORffvs.FF= 1.57, 95%CI= 1.12-2.21, p= 0.008, I2= 70.37%) and in the recessive model (ORFF+Ff vs.ff= 1.43, 95%CI= 1.08-1.89, p= 0.01, I2= 63.13%).Conclusion: In conclusion, a significant association of FokI with tuberculosis susceptibility was found in the overall analysis and in the Asian population.

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Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

Autoimmune Diseases ◽

10.1155/2012/569728 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Paola Cruz-Tapias ◽

Oscar M. Pérez-Fernández ◽

Adriana Rojas-Villarraga ◽

Alberto Rodríguez-Rodríguez ◽

María-Teresa Arango ◽

...

Keyword(s):

Risk Factor ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Genetic Characteristics ◽

Latin Americans ◽

Leukocyte Antigen

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

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Stem Cell Therapy and Regenerative Medicine in Autoimmune Diseases

10.5772/intechopen.89749 ◽

2021 ◽

Author(s):

Bhuvaneshwari Sampath ◽

Priyadarshan Kathirvelu ◽

Kavitha Sankaranarayanan

Keyword(s):

Stem Cell ◽

Immune System ◽

Regenerative Medicine ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Autoimmune Condition ◽

Recent Trends

The role of immune system in our body is to defense against the foreign bodies. However, if the immune system fails to recognize self and non-self-cells in our body leads to autoimmune diseases. Widespread autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, and more yet to be added to the list. This chapter discusses about how stem cell-based therapies and advancement of regenerative medicine endow with novel treatment for autoimmune diseases. Furthermore, in detail, specific types of stem cells and their therapeutic approach for each autoimmune condition along with their efficiency to obtain desired results are discussed. Ultimately, this chapter describes the recent trends in treating autoimmune diseases effectively using advanced stem cell research.

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Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-031850 ◽

2020 ◽

Vol 10 (5) ◽

pp. e031850 ◽

Cited By ~ 1

Author(s):

Irene B Murimi-Worstell ◽

Dora H Lin ◽

Henk Nab ◽

Hong J Kan ◽

Oluwadamilola Onasanya ◽

...

Keyword(s):

Systematic Review ◽

Systemic Lupus Erythematosus ◽

Latin American ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Damage Index ◽

Organ Damage ◽

Cochrane Library ◽

Systemic Lupus ◽

Cross Sectional

ObjectiveAt least half of patients with systemic lupus erythematosus (SLE) develop organ damage as a consequence of autoimmune disease or long-term therapeutic steroid use. This study synthesised evidence on the association between organ damage and mortality in patients with SLE.DesignSystematic review and meta-analysis.MethodsElectronic searches were performed in PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Sciences Literature for observational (cohort, case-control and cross-sectional) studies published between January 2000 and February 2017. Included studies reported HRs or ORs on the association between organ damage (measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score) and mortality. Study quality was assessed using the modified Newcastle-Ottawa assessment. Pooled HRs were obtained using the DerSimonian and Laird random-effects model. Heterogeneity was assessed using the Cochrane Q (Q) and I2 statistics.ResultsThe search yielded 10 420 articles, from which 21 longitudinal studies were selected. Most studies (85%) were of high quality. For 10 studies evaluating organ damage (SDI) as a continuous variable and reporting HR as a measure of association, a 1-unit increase in SDI was associated with increased mortality; pooled HR was 1.34 (95% CI: 1.24 to 1.44, p<0.001; Q p=0.027, I2=52.1%). Exclusion of one potential outlying study reduced heterogeneity with minimal impact on pooled HR (1.33 (95% CI: 1.25 to 1.42), p<0.001, Q p=0.087, I2=42.0%). The 11 remaining studies, although they could not be aggregated because of their varying patient populations and analyses, consistently demonstrated that greater SDI was associated with increased mortality.ConclusionsOrgan damage in SLE is consistently associated with increased mortality across studies from various countries. Modifying the disease course with effective therapies and steroid-sparing regimens may reduce organ damage, improve outcomes and decrease mortality for patients with SLE.

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