Investigation of the genetic overlap between rheumatoid arthritis and psoriatic arthritis in a Greek population

Myrthianou, E.; Zervou, M.; Budu-Aggrey, Ashley; Eliopoulos, Elias; Kardassis, Dimitris; Boumpas, DT; Kougkas, Nikolaos; Barton, Anne; Sidiropoulos, Prodromos; Goulielmos, GN

doi:10.1080/03009742.2016.1199734

Cited by 15 publications

(7 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the framework of an analysis conducted in a UK cohort by ImmunoChip array ( 7 ), TYK2 rs34536443 was not found to be associated with JIA, a result that coincides with the present data from the Greek cohort. This finding was noteworthy considering that TYK2 rs34536443 SNP was found recently, in a study performed in the Greek population ( 26 ), to exhibit a genetic overlap with PsA and RA that is well known to possess or share several similar clinical manifestations with JIA. Moreover, according to the constructed 3D model of TYK2 protein and previous observations of our group ( 26 ), it is assumed that the Pro1104Gly mutation may affect the protein's functionality by affecting elements contributing to the structural conformation of the molecule.…”

Section: Discussionmentioning

confidence: 65%

“…Aiming to gain insight to the potential structural/functional consequences of rs34536443 SNP, which has been associated with various rheumatic and other complex human diseases, we further analyzed the respective region of TYK2 protein by developing a new 3D model, improving the pre-existing one developed by Myrthianou et al ( 26 ). The rs34536443 SNP leads to the substitution of a G to a C nucleotide, thus resulting in a Pro1104Ala mutation in the TYK2 protein.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, there is still the possibility that an association of TYK2 rs34536443 with JIA may be detected if the cohort size is increased. However, given the MAF of the minor allele C of this SNP in the controls from Greece (0.22), it can be assumed that a high number of patients and controls was required to be collected (probably higher than 5,000 for each category) to obtain an 80% power of the study (at p=0.05) ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Τhe genetics of juvenile idiopathic arthritis: Searching for new susceptibility loci

Zervou

Dimopoulou

Eliopoulos

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Juvenile idiopathic arthritis (JIA) is an autoimmune disease that is characterized by persistent chronic arthritis and affected by genetic and environmental factors. Different genetic variations have been reported as risk factors for JIA. However, given that many results could not be replicated in individuals of different ancestral origin, it was assumed that heterogeneous genetic factors are involved in this disease. In the present study, we analyzed three single nucleotide polymorphisms (SNPs), namely PTPRC (rs10919563), TYK2 (rs34536443) and PRKCQ (rs4750316), which were found to be associated with JIA in previous studies. We also investigated whether the intron-4 located 27-bp VNTR of endothelial nitric oxide synthase (eNOS), is associated with risk for JIA in Greece. In total, 125 JIA patients and 221 healthy controls from northern Greece were included in the study as a sample set. Samples were then analyzed, and genotyped for the three SNPs with TaqMan primer-probe sets, using a Real-Time PCR platform (ViiA™ 7 Real-Time PCR system), while eNOS VNTR polymorphism was genotyped by PCR. Statistical analysis was performed using a GraphPad Prism statistical program. The χ2 test was used to examine differences of genotype and allele frequencies between patients and controls. Statistical significance was defined by using the two-tailed P<0.05 test. Bioinformatics analysis was conducted by using BlastP, Pymol, Maestro and Desmond. In the case-control association study performed, eNOS only was found to be associated with JIA. Genotype a/a and allele ‘a’ were found in a higher frequency in JIA patients than in controls [p<0.0001, odds ratio (OR)=0.15, 95% confidence intervals (CI): 0.065–0.37; and p<0.0001, OR=0.34, 95% CI: 0.23–0.49, respectively]. No associations with JIA were detected for TYK2, PTPRC or PRKCQ. Aiming to investigate the structural consequences and the structure/function relationships accompanying the Pro1104 to Ala (rs34536443) mutation on TYK2 protein, bioinformatics analysis was performed. Combining three-dimensional (3D)-modeling and molecular dynamics simulations we identified changes in structural flexibility, affecting the functionality of the kinase domain of TYK2. To the best of our knowledge, this is the first time that eNOS VNTR polymorphism is associated with susceptibility to JIA, suggesting a differential role of allele ‘a’ in various complex diseases. The current data emphasize the importance of comparative studies in populations of a different ancestral background towards the clarification of the role of specific alleles in the development of JIA.

show abstract

Section: Discussionmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Τhe genetics of juvenile idiopathic arthritis: Searching for new susceptibility loci

Zervou

Dimopoulou

Eliopoulos

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…Notably, 13 of these genes were involved in the pathogenesis of RA in previous studies. Several genes, such as PLCL2 , COG6 , RIF5 , ARID5B, and CCR6, were reported to be the susceptibility loci for RA [ 20 - 22 ]. Chemokine (C-C motif) receptor 6 gene (CCR6) encodes an important protein that is expressed in memory T-cells and immature dendritic cells and plays a critical role in B-cell maturation and differentiation [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Pleiotropic Genes for Immune and Skeletal Diseases Using Multivariate MetaCCA Analysis

Cao

Dèng

et al. 2021

View full text Add to dashboard Cite

Background: Immune and skeletal systems physiologically and pathologically interact with each other. The immune and skeletal diseases may share potential pleiotropic genetics factors, but the shared specific genes are largely unknown Objective: This study aimed to investigate the overlapping genetic factors between multiple diseases (including rheumatoid arthritis (RA), psoriasis, osteoporosis, osteoarthritis, sarcopenia and fracture) Methods: The canonical correlation analysis (metaCCA) approach was used to identify the shared genes for six diseases by integrating genome-wide association study (GWAS)-derived summary statistics. Versatile Gene-based Association Study (VEGAS2) method was further applied to refine and validate the putative pleiotropic genes identified by metaCCA. Results: About 157 (p<8.19E-6), 319 (p<3.90E-6) and 77 (p<9.72E-6) potential pleiotropic genes were identified shared by two immune disease, four skeletal diseases, and all of the six diseases, respectively. The top three significant putative pleiotropic genes shared by both immune and skeletal diseases, including HLA-B, TSBP1 and TSBP1-AS1 (p<E-300) were located in the major histocompatibility complex (MHC) region. Nineteen of 77 putative pleiotropic genes identified by metaCCA analysis were associated with at least one disease in the VEGAS2 analysis. Specifically, majority (18) of these 19 putative validated pleiotropic genes were associated with RA. Conclusion: The metaCCA method identified some pleiotropic genes shared by the immune and skeletal diseases. These findings help to improve our understanding of the shared genetic mechanisms and signaling pathways underlying immune and skeletal diseases.

show abstract

“…Regarding non‐HLA genes, STIP1 is a possible biological marker in patients with PsA; 65 however, there are few reports concerning the role of STIP1 in the pathogenesis of the disease and its role in PsA has not been fully elucidated. The genes HCP5 , 66 CD226 , 67 PRL , 68 and CYP1A1 69 are only associated with PsA, but their actual role in the pathogenesis of the disease is unknown. Therefore, the number of susceptibility genes of PsA is still unclear, and many questions concerning the role of non‐HLA genes in PsA still need to be addressed.…”

Section: Discussionmentioning

confidence: 99%

Psoriatic arthritis: A systematic review of non‐HLA genetic studies and important signaling pathways

et al. 2020

View full text Add to dashboard Cite

Psoriatic arthritis (PsA) is a chronic inflammatory disease that primarily invades the musculoskeletal system and skin. 1 Usually, besides the arthritis damage, including arthritis, enthesitis, dactylitis and axial involvement, patients with PsA have psoriatic skin, such as epidermal hyperplasia, hyperkeratosis, parakeratosis, Munro's microabscesses and mixed dermal infiltrates. 2 In general, the severity of a patient's joint symptoms is consistent with the severity of the skin lesions. 3 In some cases, patients with PsA without psoriatic skin features only have arthritis damage or finger pain, which is similar to rheumatoid arthritis (RA). Generally, only about 13% of patients with PsA have rheumatoid factor in the blood and synovial fluid, while more than 80% of RA patients can be detected with rheumatoid factor. 4 The prevalence of PsA around the world is 0.3%-1%, 4 which differs in race and regions. In Western countries, the prevalence rates are about 0.02%, 0.42% and 0.25% in Sweden, Italy and the USA respectively, 5,6 whereas the rates are relatively lower in the Eastern countries, ranging from 0.01% to 0.1% in China, and <0.00001% in Japan. 6 PsA is not only harmful to an individual's health and life quality, but also may lead to a higher risk to suffer from cardiovascular events. 7 The pathogenesis of PsA is complex, and itmay be caused by genetic and environmental factors. Environmental aspects include infections (eg infectious diarrhea, human immunodeficiency virus infection), smoking, trauma and obesity. 8-11 In the researches for susceptibility genes for PsA, some human leukocyte antigen (HLA) genes are found as risk factors, and some HLA genes are found as protect factors. For instances, HLA-B*38 and HLA-Cw6 alleles are

show abstract

Investigation of the genetic overlap between rheumatoid arthritis and psoriatic arthritis in a Greek population

Cited by 15 publications

References 63 publications

Τhe genetics of juvenile idiopathic arthritis: Searching for new susceptibility loci

Τhe genetics of juvenile idiopathic arthritis: Searching for new susceptibility loci

Identification of Potential Pleiotropic Genes for Immune and Skeletal Diseases Using Multivariate MetaCCA Analysis

Psoriatic arthritis: A systematic review of non‐HLA genetic studies and important signaling pathways

Contact Info

Product

Resources

About