scholarly journals NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis

2010 ◽  
Vol 70 (4) ◽  
pp. 668-674 ◽  
Author(s):  
P Dieudé ◽  
M Guedj ◽  
J Wipff ◽  
B Ruiz ◽  
G Riemekasten ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Systemic Sclerosis ◽  
Potential Role ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Fibrosing Alveolitis ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Caucasian Origin

BackgroundRecent evidence has highlighted a potential role of interleukin 1β (IL-1β) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1β. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders.ObjectiveTo study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population.MethodsNLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin.ResultsConditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA.ConclusionsOur results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.

scholarly journals The Potential Role of Genetic Markers in Talent Identification and Athlete Assessment in Elite Sport

Sports ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 88 ◽  
Author(s):  
Ysabel Jacob ◽  
Tania Spiteri ◽  
Nicolas Hart ◽  
Ryan Anderton
Keyword(s):  
Genetic Markers ◽  
Skill Acquisition ◽  
Athletic Performance ◽  
Potential Role ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Talent Identification ◽  
Motor Skill Acquisition ◽  
Athletic Ability

In elite sporting codes, the identification and promotion of future athletes into specialised talent pathways is heavily reliant upon objective physical, technical, and tactical characteristics, in addition to subjective coach assessments. Despite the availability of a plethora of assessments, the dependence on subjective forms of identification remain commonplace in most sporting codes. More recently, genetic markers, including several single nucleotide polymorphisms (SNPs), have been correlated with enhanced aerobic capacity, strength, and an overall increase in athletic ability. In this review, we discuss the effects of a number of candidate genes on athletic performance, across single-skilled and multifaceted sporting codes, and propose additional markers for the identification of motor skill acquisition and learning. While displaying some inconsistencies, both the ACE and ACTN3 polymorphisms appear to be more prevalent in strength and endurance sporting teams, and have been found to correlate to physical assessments. More recently, a number of polymorphisms reportedly correlating to athlete performance have gained attention, however inconsistent research design and varying sports make it difficult to ascertain the relevance to the wider sporting population. In elucidating the role of genetic markers in athleticism, existing talent identification protocols may significantly improve—and ultimately enable—targeted resourcing in junior talent pathways.

Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population

2010 ◽  
Vol 69 (11) ◽  
pp. 1958-1964 ◽  
Author(s):  
P Dieudé ◽  
M Guedj ◽  
J Wipff ◽  
B Ruiz ◽  
G Riemekasten ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Meta Analysis ◽  
Genetic Disorders ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Caucasian Origin ◽  
Pulmonary Arterial ◽  
Inflammatory Signalling ◽  
Intron 2 ◽  
Genetic Susceptibility Factor

BackgroundTNFAIP3 encodes the ubiquitin-modifying enzyme, a key regulator of inflammatory signalling pathways. Convincing associations between TNFAIP3 variants and autoimmune diseases have been reported.ObjectiveTo investigate the association of TNFAIP3 polymorphisms with systemic sclerosis (SSc).MethodsThree single nucleotide polymorphisms (SNPs) in a set of 1018 patients with SSc and 1012 controls of French Caucasian origin were genotyped. Two intergenic SNPs, rs10499194 and rs6920220, and one located in TNFAIP3 intron 2, rs5029939, were selected. The TNFAIP3 rs5029939 found to be associated with SSc in this first set was then genotyped in a second set of 465 patients with SSc and 182 controls from Germany and 184 patients with SSc and 124 controls from Italy. Pooled odd ratios were calculated by Mantel–Haenszel meta-analysis.ResultsThe rs5029939 G allele was found to be significantly associated with SSc susceptibility (pooled OR=2.08 (95% CI 1.59 to 2.72); p=1.16×10−7), whereas the rs10499194 and rs6920220 variants displayed no association. Only one of the predicted haplotypes investigated in the French sample was significantly associated with SSc (p=8.91×10−8), and this haplotype was discriminating only in the presence of the rs5029939 risk allele, suggesting that this SNP tags the association signal. The strongest associations of rs5029939 with subphenotypes, having large magnitudes for complex genetic disorders, were observed for diffuse cutaneous SSc (pooled OR=2.71 (1.94 to 3.79), p=5.2×10−9), fibrosing alveolitis (pooled OR=2.26 (1.61 to 3.17), p=2.5×10−6) and pulmonary arterial hypertension (pooled OR=3.11 (1.86 to 5.17), p=1.3×10−5).ConclusionThese results suggest that TNFAIP3 is a genetic susceptibility factor for SSc.

scholarly journals Detection of single nucleotide polymorphisms at major prolificacy genes in the Mehraban sheep and association with litter size

2018 ◽  
Vol 18 (3) ◽  
pp. 685-698 ◽  
Author(s):  
Reza Talebi ◽  
Ahmad Ahmadi ◽  
Fazlollah Afraz ◽  
Julien Sarry ◽  
Florent Woloszyn ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Litter Size ◽  
Potential Role ◽  
Chromosome 6 ◽  
The Novel ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hardy Weinberg Equilibrium ◽  
Gdf9 Gene

Abstract The present study aimed to investigate the presence of polymorphisms at four known genes controlling ovine prolificacy i.e. BMP15, GDF9, BMPR1B and B4GALNT2 in a sample of 115 Iranian Mehraban ewes and their association with litter size (LS) and lambs’ birth weight (BW) traits. Using Sanger sequencing of exons and polymorphism specific genotyping, ten SNPs (Single Nucleotide Polymorphisms) were observed in only two genes, GDF9 and BMPR1B. Seven SNPs were found in the GDF9 gene on the chromosome 5. Among them, six were already described in the coding sequence, and a new one (g.41840985C>T) was found in the 3’UTR. In the BMPR1B gene on the chromosome 6, three novel SNPs were detected in the exon 7 (g.29382184G>A; g.29382337G>A and g.29382340G>A). Allelic frequencies were established for six SNPs among the ten identified and they were in Hardy-Weinberg equilibrium. A significant association was found between the novel SNPs found in the exon 7 of BMPR1B and LS. Present results indicate the potential role of the BMPR1B locus in controlling prolificacy of Mehraban sheep and provide genetic markers for further exploitation in selection to improve reproductive efficiency.

scholarly journals The Role of Bacteria and Pattern Recognition Receptors in GvHD

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
E. Holler ◽  
K. Landfried ◽  
J. Meier ◽  
M. Hausmann ◽  
G. Rogler
Keyword(s):  
Innate Immunity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Long Time ◽  
Potential Risk Factors ◽  
Pathogen Recognition Receptors ◽  
Antigen Presenting ◽  
Molecular Patterns ◽  
Gastrointestinal Decontamination

Graft-versus-Host Disease (GvHD) is the most serious complication of allogeneic stem cell transplantation (SCT) and results from an activation of donor lymphocytes by recipient antigen-presenting cells (APCs). For a long time, it has been postulated that the intestinal microflora and endotoxin exert a crucial step in this APC activation, as there is early and severe gastrointestinal damage induced by pretransplant conditioning. With the detailed description of pathogen-associated molecular patterns and pathogen recognition receptors single nucleotide polymorphisms of TLRs and especially NOD2 have been identified as potential risk factors of GvHD and transplant related complications thus further supporting the crucial role of innate immunity in SCT, related complications. Gastrointestinal decontamination and neutralization of endotoxin have been used to interfere with this early axis of activation with some success but more specific approaches of modulation of innate immunity are needed for further improvement of clinical outcome.

An Analysis of the Association between Epilepsy-Related Genes and Vertigo in the Polish Population

2018 ◽  
Vol 23 (3) ◽  
pp. 135-144
Author(s):  
Katarzyna Pawlak-Osińska ◽  
Katarzyna Linkowska ◽  
Karolina Hołub ◽  
Katarzyna Winiarska ◽  
Bartosz Stankiewicz ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Background ◽  
Potential Role ◽  
Control Group ◽  
Polish Population ◽  
Nucleotide Polymorphisms ◽  
Chromosome 11 ◽  
Single Nucleotide

Considering the possibility of a common genetic background of vertigo and epilepsy, we genotyped an affected group of individuals with vertigo and an unaffected group, by studying 26 single-nucleotide polymorphisms (SNPs) in 14 genes which were previously reported to be of particular importance for epilepsy. Significant differences were found between the patients and the control group (χ2 = 38.3, df = 3, p = 1.6 × 10–7) for the frequencies of haplotypes consist ing of 2 SNPs located in chromosome 11 (rs1939012 and rs1783901 within genes MMP8 and SCN3B, respectively). The haplotype rs1939012:C-rs1783901:A, consisting of the minor-frequency alleles was found to be associated with a higher risk of vertigo (OR = 5.0143, 95% CI = 1.6991–14.7980, p = 0.0035). In contrast, the haplotype rs1939012:T-rs1783901:A showed a significant association with a decreased risk of the disease (OR = 0.0597, 95% CI = 0.0136–0.2620, p = 0.0002). Our results suggest that the SNPs rs1939012 and rs1783901 may play a potential role of gene regulation and/or epistasis in a complex etiology of vertigo.

scholarly journals A Replication Study from Chinese Supports Association between Lupus-Risk Allele inTNFSF4and Renal Disorder

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Xu-jie Zhou ◽  
Fa-juan Cheng ◽  
Yuan-yuan Qi ◽  
Ming-hui Zhao ◽  
Hong Zhang
Keyword(s):  
Lupus Nephritis ◽  
Renal Biopsy ◽  
Chinese Population ◽  
Renal Involvement ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Renal Disorder ◽  
Risk Alleles ◽  
Genome Wide

A recent phenotypic association study of genetic susceptibility loci in SLE suggested thatTNFSF4gene might be useful to predict renal disorder in lupus patients. To replicate the association, two single-nucleotide polymorphisms (SNPs: rs2205960 and rs10489265) were genotyped in 814 SLE patients. Correlations between genotypes andTNFSF4expression were determined. The stainings ofTNFSF4in renal biopsy specimens were checked by immunohistochemistry. The SNPs ofTNFSF4were associated with renal involvement in lupus patients from the Chinese population (Pvalues for rs2205960 and rs10489265 were 0.014 and 0.005 in additive model, resp.). An association between risk genotypes and low C3 levels was also observed (P=0.034). Functional prediction suggested that rs2205960 had a regulatory feature. The risk alleles seemingly correlated with lowerTNFSF4expression. StrongTNFSF4expression was detected in lymph nodes and “apparently normal” paratumor renal biopsy but not in renal biopsies from lupus nephritis. In genome-wide expression data,TNFSF4was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies. However, the associations were marginally significant. Our data firstly replicated the association ofTNFSF4with renal disorder in SLE patients in the Chinese population, which supported thatTNFSF4may act as a marker of lupus nephritis. The detailed mechanisms of its role in pathogenesis will still be further needed.

scholarly journals Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

2010 ◽  
Vol 70 (3) ◽  
pp. 454-462 ◽  
Author(s):  
LM Diaz-Gallo ◽  
P Gourh ◽  
J Broen ◽  
C Simeon ◽  
V Fonollosa ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Meta Analysis ◽  
The Novel ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Independent Replication ◽  
First Time

ObjectiveTwo functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes.Methods3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc.ResultsThe meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (pFDRcorrected=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (pFDRcorrected=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (pFDRcorrected=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1).ConclusionThe study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.

Single nucleotide polymorphisms in innate immunity genes: abundant variation and potential role in complex human disease

2002 ◽  
Vol 190 (1) ◽  
pp. 9-25 ◽  
Author(s):  
Ross Lazarus ◽  
Donata Vercelli ◽  
Lyle J. Palmer ◽  
Walt J. Klimecki ◽  
Edwin K. Silverman ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Single Nucleotide Polymorphisms ◽  
Human Disease ◽  
Potential Role ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Complex Human Disease ◽  
Immunity Genes
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