Novel Risk Loci for Rheumatoid Arthritis in Han Chinese and Congruence With Risk Variants in Europeans

Jiang, Lei; Yin, Jian; Ye, Lingying; Yang, Jian; Hemani, Gibran; Liu, Aijun; Zou, Hejian; He, Dongyi; Sun, Lingyun; Zeng, Xiaofeng; Li, Zhanguo; Zheng, Yi; Lin, Yiping; Liu, Yi; Fang, Yongfei; Xu, Jianhua; Li, Yinong; Dai, Sheng‐Ming; Guan, Jian-Long; Jiang, Lindi; Wei, Qianghua; Wang, Yi; Yang, Li; Huang, Cibo; Zuo, Xiaoxia; Liu, Yu; Wu, Xin; Zhang, Libin; Zhou, Ling; Zhang, Qing; Li, Ting; Chen, Ling; Xu, Zhen; Yang, Xiaoping; Feng, Qian; Xie, Weilin; Liu, Wei; Guo, Qian; Huang, Shaolan; Zhao, Jing Hua; Li, Mengmeng; Jin, Yanhua; Gao, Jie; Lv, Ying; Wang, Yiwen; Li, Lin; Guo, Aihua; Danoy, Patrick; Willner, Dana; Cremin, Catherine; Hadler, Johanna; Zhang, Fengchun; Zhao, Yan; Li, Mengtao; Yue, Tao; Fan, Xiaolei; Guo, Jianping; Mu, Rong; Li, Jingyi; Wu, Chao; Zeng, Ming; Wang, Jiucun; Li, Shilin; Jin, Li; Wang, Binbin; Wang, Jing; Ma, Xu; Sun, Liangdan; Zhang, Xuejun; Brown, Matthew A.; Visscher, Peter M.; Su, Ding‐Feng; Xu, Huji

doi:10.1002/art.38353

Cited by 73 publications

(61 citation statements)

References 44 publications

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“…In contrast, the risks of developing an autoimmune disease such as RA seems to be lower upon treatment with DPP4 inhibitors, according to epidemiological studies [136]. A single nucleotide polymorphism (SNP) within an intron of DPP4 has been identified recently as a novel risk locus of RA [137]. However, in-vivo studies with three different DASH inhibitors ameliorated disease symptoms in both wild-type as well as DPP4-deficient F344 rats, implying the involvement of additional DPP4-like enzymes [111].…”

Section: Asthmamentioning

confidence: 99%

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Wagner¹,

Klemann²,

Stephan

et al. 2016

Clinical and Experimental Immunology

107

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SummaryDipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline-specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins. Apart from DPP4, DASH proteins include fibroblast activation protein alpha (FAP), DPP8, DPP9, DPP4-like protein 1 (DPL1, DPP6, DPPX L, DPPX S), DPP4-like protein 2 (DPL2, DPP10) from the DPP4-gene family S9b and structurally unrelated enzyme DPP2, displaying DPP4-like activity. In contrast, DPP6 and DPP10 lack enzymatic DPP4-like activity. These DASH proteins play important roles in the immune system involving quiescence (DPP2), proliferation (DPP8/DPP9), antigen-presenting (DPP9), costimulation (DPP4), T cell activation (DPP4), signal transduction (DPP4, DPP8 and DPP9), differentiation (DPP4, DPP8) and tissue remodelling (DPP4, FAP). Thus, they are involved in many pathophysiological processes and have therefore been proposed for potential biomarkers or even drug targets in various cancers (DPP4 and FAP) and inflammatory diseases (DPP4, DPP8/DPP9). However, they also pose the challenge of drug selectivity concerning other DASH members for better efficacy and/or avoidance of unwanted side effects. Therefore, this review unravels the complex roles of DASH proteins in immunology.Keywords: antigen presentation/processing, CD26, co-stimulation, DPP4 activity and/or structure homologue proteins (DASH), signal transductionThe dipeptidyl peptidase (DPP)4 family of DPP4 activity and/or structure homologue (DASH) proteins Within the last two decades a number of enzymes have been discovered to also display DPP4-like activity or are structural homologues to DPP4. These enzymes/proteins are referred to as DPP4 activity and/or structure homologue (DASH) proteins, and can be grouped into the DPP4 gene family and non-related DPP4-like enzymes. Except for DPL1 and DPL2, all members display DPP4-like activity with neutral to basic pH optima and similar inhibition profiles [6,7]. DPP4 (CD26). DPP4 (CD26) is the best-known DASH protein and has been described in detail elsewhere [7][8][9].

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Section: Asthmamentioning

confidence: 99%

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Wagner¹,

Klemann²,

Stephan

et al. 2016

Clinical and Experimental Immunology

107

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“…The CCR6 gene rs1854853 association was first discovered in a study on a Han Chinese population [13], as the G allele of this polymorphism was associated with the decreased risk of RA. Moreover, genotypes rs1854853 depicted a strong association with Anti-CCP-positive, but not with Anti-CCP-negative RA patients [13].…”

Section: Discussion ____________________________mentioning

confidence: 99%

“…By producing IL-17, a well-known inflammatory cytokine in most autoimmune diseases, Th17 cells play an important role in the pathogenesis of RA [11]. According to studies conducted on RA, some important risk alleles which impact the immune [13,14]. In addition to RA, CCR6 gene SNPs have been associated with Crohn's disease, colorectal cancer, Graves' disease, and psoriasis [15][16][17].…”

Section: Introduction __________________________mentioning

confidence: 99%

“…A metaanalysis indicated that the CCR6 gene rs1854853 SNP was associated with an increased risk of RA in different populations [18]. Moreover, a GWAS reported the strong association of rs1854853 with the risk of RA in Han Chinese and European white populations as well as with the clinical outcomes of the disease [13].…”

Section: Introduction __________________________mentioning

confidence: 99%

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Association study of CCR6 gene single nucleotide polymorphism with susceptibility to rheumatoid arthritis in Iranian population

et al. 2018

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Several genome-wide association studies (GWASs) have identified numerous susceptibility genes for risk of rheumatoid arthritis (RA). Moreover, a bulk of the individual association studies in various populations has disclosed that genetics are significantly responsible for RA pathogenesis. CCR6 is a chemokine which is involved in the infiltration of inflammatory cells to sites of immune response. In this study, the association of CCR6 gene rs1854853 single nucleotide polymorphism (SNP) with susceptibility to RA was evaluated in an Iranian population. The investigated population comprised 250 RA patients and 500 healthy individuals. Real time TaqMan MGB-based PCR allelic discrimination approach was employed to genotype the samples with regard to the CCR6 gene rs1854853 SNP. Considering the A allele of rs1854853 SNP as reference, the G allele did not demonstrate a different prevalence between RA patients and controls (p= 0.17). Moreover, AG and GG genotypes were almost equally distributed between cases and controls (p= 0.61 and 0.14, respectively). Alternately, the dominant model of AG+GG had no significant difference in frequency between the study groups (p= 0.36). However, genotypes did show a correlation with the clinicopathological specifications of RA patients. Results suggest that the CCR6 gene rs1854853 SNP is not involved in the genetic pathogenesis of RA in the Iranian population.

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“…9,14 An association of sprouty-related EVH1 domain-containing protein 2 (SPRED2) locus was reported in an expanded meta-analysis of six genome-wide association studies in anticyclic citrullinated peptide antibody (anti-CCP)-positive RA patients in Caucasians. 15 In a genome-wide association study of a Han population, 16 the top SNPs at the three nonmajor histocompatibility complex (non-MHC) loci were associated with both ACPA-positive and -negative RA, but the association signals were all stronger in ACPA-positive patients than in ACPA-negative patients. In the same study, the C-C chemokine receptor type 6 variants showed strong association in ACPA-positive RA patients but not in ACPA-negative RA patients, which is consistent with previous studies in White Europeans.…”

Section: Genetic Factors Predisposing To Clinical Subsets Of Acpa-posmentioning

confidence: 99%

Genetic markers and clinical relevance in rheumatoid arthritis

Guo

2015

Int J of Rheum Dis

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Novel Risk Loci for Rheumatoid Arthritis in Han Chinese and Congruence With Risk Variants in Europeans

Cited by 73 publications

References 44 publications

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Association study of CCR6 gene single nucleotide polymorphism with susceptibility to rheumatoid arthritis in Iranian population

Genetic markers and clinical relevance in rheumatoid arthritis

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