A complex role of anthrax toxin receptor 2 polymorphisms and capillary morphogenesis protein 2 in ankylosing spondylitis pathogenesis

Zhang, Zhijian; Yu, Kun; Dai, Dongfa; Yuan, Fang; Liang, Fei; Liu, Nan; Yang, Xi; Sun, Yuying

doi:10.1007/s10067-015-3158-9

Cited by 3 publications

(3 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results also demonstrated a weak association for the rs6534639 genotype AA with the AS + AAU + group but not with the AS + AAU − group. The rs6534639 genotype CC was reported to be associated with AS by a previous study from China [ 15 ]. Due to the obvious heterogeneity, the meta-analysis failed to find an association of this SNP with AS in all studies or in the Chinese population.…”

Section: Discussionmentioning

confidence: 99%

Case-Control Study and Meta-Analysis Show a Weak Association between ANTXR2 Polymorphisms and Ankylosing Spondylitis in Chinese Han

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Previous studies have demonstrated associations of ANTXR2 gene polymorphisms with ankylosing spondylitis (AS). These associations differ depending on the ethnic populations and AS subgroups studied. Purposes of the current study were to evaluate the associations of 4 single nucleotide polymorphisms (SNPs) of the ANTXR2 gene with susceptibility to AS alone or AS in combination with acute anterior uveitis (AAU) in Chinese Han. Therefore, a case-control association study was performed in 880 AS+AAU−, 860 AS+AAU+, and 1700 healthy controls. Genotyping was performed using the iPLEXGold genotyping assay. Our results showed a weak association of rs6534639 AA genotype with AS+AAU+ patients (p=0.042), which was lost after correction for multiple comparisons. No other association was found between SNPs of ANTXR2 and susceptibility of AS+AAU− or AS+AAU+. A meta-analysis was performed to evaluate the associations of polymorphisms in the ANTXR2 gene with AS. Results showed a weak association of rs4389526 with AS susceptibility in all studies but failed to show an association of rs6534639 with AS in Chinese Han. Taken together, this study shows no association between ANTXR2 polymorphisms and AS susceptibility in a Chinese Han population, but meta-analysis showed that rs4389526 in the ANTXR2 gene was weakly associated with AS susceptibility in both Caucasian and Chinese Han patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Case-Control Study and Meta-Analysis Show a Weak Association between ANTXR2 Polymorphisms and Ankylosing Spondylitis in Chinese Han

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…In Han Chinese, SNPs rs4690127 , rs6823031 , and rs4333130 in the ANTXR2 gene correlate with AS. Genetic variations in ANTXR2 downregulate its expression, possibly increasing capillary permeability and inducing inflammation in AS 28 …”

Section: Figurementioning

confidence: 99%

“…Genetic variations in ANTXR2 downregulate its expression, possibly increasing capillary permeability and inducing inflammation in AS. 28 G protein-coupled receptors (GPRs) play diverse roles in cell signaling. GPR35, GPR37, and GPR65 are associated with AS.…”

mentioning

confidence: 99%

Genetic risk factors in ankylosing spondylitis: Insights into etiology and disease pathogenesis

Mathew,

Bhagavaldas,

Biswas

et al. 2023

Int J of Rheum Dis

View full text Add to dashboard Cite

Ankylosing spondylitis (AS) is a complex inflammatory condition within the spectrum of spondyloarthropathies (SpAs). HLA-B*27, IL-17, IL-23, and complex pathways drive AS progression. Microbiota, ERAPs, and TLRs also contribute to AS. This editorial delves into AS genetics, unraveling its molecular underpinnings. Since its discovery in 1973, HLA-B*27's association with AS has been extensively studied. About 90%-95% of AS patients carry HLA-B*27, yet only 1%-2% develop AS. This highly polymorphic allele includes subtypes like HLA-B*27:02, B*27:04, and B*27:05, showing variable associations across populations. Hypotheses include the "arthritogenic peptide" and "molecular mimicry," suggesting unique peptide presentation or microbial triggers. 1,2 Killer cell immunoglobulin-like receptors (KIRs) expressed by NK and T cells regulate immunity via inhibitory and activating signals and are key players in AS by engaging HLA-B*27. KIR-HLA variations may impact SpAs. Balancing activating and inhibitory KIR-HLA genotypes might influence AS susceptibility. KIR3DS1 allele frequency is elevated with HLA-B*27, while KIR3DL1, its inhibitory counterpart, is reduced in AS. Both interact with Bw4 epitope-bearing HLA-B alleles. B27 2 homodimers bind KIR3DL1, KIR3DL2, and LILRB2, impacting inflammatory responses (Figure 1A). 3 KIR3DL2 ligation inhibits IFNγ production and boosts IL-17, linking NK cells and CD4+ T cells to AS. 4 While KIR3DS1's ligand is not yet known, AS patients show elevated KIR3DL2 + CD4 + T cells producing IL-17, linking them to disease progression. This intricate interplay underscores KIR-HLA's role in shaping AS immunopathology.Crucial antigenic peptides, vital for immune recognition, undergo a refining via endoplasmic reticulum aminopeptidases (ERAP1 and ERAP2). ERAP1 fine-tunes peptides to 8-10 amino acids, while ERAP2 prefers shorter variants (7-8-mers). 5,6 ERAPs also influence cytokine receptor shedding, cytokine signaling, angiogenesis, and macrophage activation. 7 Their intricate association with AS involves HLA-B*27, evident in both positive and negative cases. ERAP1, combined with HLA-B*27, significantly influences familial AS risk. ERAP1 SNPs like rs30187, rs2287987, rs10050860, rs17482078, and rs27044 alter peptide interactions with HLA-B*27, shaping T-cell responses. 8 Some ERAP1 variants offer protection via peptide trimming. 9 Some

show abstract

Identification of the miRNA–mRNA regulatory network in multiple sclerosis

Yang

Wei

Qian

2016

Neurological Research

View full text Add to dashboard Cite

show abstract

A complex role of anthrax toxin receptor 2 polymorphisms and capillary morphogenesis protein 2 in ankylosing spondylitis pathogenesis

Cited by 3 publications

References 30 publications

Case-Control Study and Meta-Analysis Show a Weak Association between ANTXR2 Polymorphisms and Ankylosing Spondylitis in Chinese Han

Case-Control Study and Meta-Analysis Show a Weak Association between ANTXR2 Polymorphisms and Ankylosing Spondylitis in Chinese Han

Genetic risk factors in ankylosing spondylitis: Insights into etiology and disease pathogenesis

Identification of the miRNA–mRNA regulatory network in multiple sclerosis

Contact Info

Product

Resources

About