Polymorphism in MICA rather than HLA-B/C genes is associated with psoriatic arthritis in the Jewish population

González, Segundo; Brautbar, Chaim; Martínez‐Borra, Jesús; López-Vázquez, Antonio; Segal, Refael; Blanco-Gelaz, Miguel Ángel; Enk, Claes D.; Safriman, Cilly; López‐Larrea, Carlos

doi:10.1016/s0198-8859(01)00242-7

Cited by 78 publications

(71 citation statements)

References 26 publications

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“…Although, the exact gene(s) involved in genetic susceptibility have not been identiWed, some candidate genes are located on chromosome 6p [11,12,33,34]. However, these genes are too distant from the ACE gene (17q23) to explain the association observed.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme gene polymorphism in patients with psoriatic arthritis

et al. 2007

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To investigate the frequency of angiotensinconverting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in adults with psoriatic arthritis (PsA), a heterogeneous chronic disease with autoimmune pathology. ACE gene I/D polymorphism inXuences the plasma and tissue levels of ACE and has an involvement in inXammatory mechanism. The frequency of ACE gene I/D polymorphism genotypes was determined in 51 adults with PsA from Kuwait, and compared to that in 100 ethnically matched healthy controls using polymerase chain reaction. The distribution of ACE I/D polymorphism and allele frequencies in PsA patients were not signiWcantly diVerent from controls (P > 0.05). Further analyses of PsA patients showed that ACE I/D gene polymorphism was not associated with family history, clinical manifestations, and disease severity. However, the frequency of II genotype was signiWcantly higher in patients with late disease onset than in those with early onset (25 vs. 3%; P = 0.04). No diVerence was found between the distribution of the ACE genotype in PsA patients and the general population in Kuwait.However, the presence of II genotype may confer susceptibility to the development of late onset PsA.

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Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme gene polymorphism in patients with psoriatic arthritis

et al. 2007

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“…For example, increased frequency of MICA A6 allele was found in patients with oral squamous cell carcinoma (Liu et al, 2002), Behcet's disease (Molinotti et al, 2001), and ulcerative colitis (Sugimura et al, 2001). In addition, increased frequency of A9 allele was reported in psoriatic arthritis (Gonzalez et al, 2001) and type I diabetes (Lee et al, 2000).…”

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The increase of MICA gene A9 allele associated with gastric cancer and less schirrous change

Lee

et al. 2004

Br J Cancer

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Since surgical resection is the principal treatment of gastric cancer, early detection is the only effective strategy against this disease at present. Recently, a new polymorphic gene family, the major histocompatibility complex class I chain-related (MIC) genes located about 40 kb centromeric to HLA-B gene has been proposed. This family consists of five genes (A, B, C, D and E). Among them, MICA has five various alleles (A4, A5, A5.1, A6 and A9), which can be used as a polymorphic marker for genetic mapping and for disease susceptibility. The MICA polymorphism was studied in our gastric cancer patients to see if there is any possible correlation with genetic predisposition and clinicopathological factors. Genomic DNA was extracted from fresh or frozen peripheral blood leukocytes in 107 patients with gastric adenocarcinoma who underwent gastrectomy in our hospital and 351 noncancer controls. MICA polymorphism was analysed by using PCR-based technique. The results showed both phenotypic and allele frequencies of allele A9 in patients with gastric cancer were significantly higher than controls (33 vs 17.6%, P ¼ 0.005; 17 vs 9.9%, P ¼ 0.02). Gastric adenocarcinoma with allele A9 was associated with less schirrous change than those without (P ¼ 0.014). MICA gene A9 allele might confer the risk of gastric cancer and associate with less schirrous change. The mechanisms among them deserve further investigation.

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“…Furthermore, though not reaching statistical significance, all patients with LGL leukemia were found to have a high proportion of low-affinity extracellular domains, suggesting that modulated binding of MICA to NKG2D may be a feature of the pathophysiology of this leukemia. 24,29,30 Pathological activity of this pathway has been implicated in various autoimmune conditions and several MICA alleles have been associated with particular autoimmune diseases [31][32][33][34] as well as a genetic predisposition to certain types of tumor. [35][36][37][38] To date, the inciting antigen driving T-cell clonal expansions in LGL leukemia has not been found, but certainly either the breakdown of self-tolerance or the addition of a tumor burden could be postulated to be operative in LGL leukemia.…”

Section: Discussionmentioning

confidence: 99%

MICA polymorphism identified by whole genome array associated with NKG2D-mediated cytotoxicity in T-cell large granular lymphocyte leukemia

Viny¹,

Clemente²,

Jasek³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundLarge granular lymphocyte leukemia is a semi-autonomous clonal proliferation of cytotoxic T cells accompanied by immune cytopenias and various autoimmune conditions. Due to the rarity of this disease and its association with autoimmune diseases, a theoretical germline or somatic mutation might have significant penetrance, thus enabling detection, even from samples of suboptimal size, through genome-wide association studies. Design and MethodsTo investigate a non-mendelian genetic predisposition to large granular lymphocyte leukemia, we used a step-wise method for gene discovery. First, a modified 'random forests' technique was used for candidate gene identification: this was followed by traditional allele-specific polymerase chain reaction, sequencing modalities, and mechanistic assays. ResultsOur analysis found an association with MICA, a non-peptide-presenting, tightly regulated, stress-induced MHC-like molecule and cognate receptor for NKG2D, found abundantly on large granular lymphocyte leukemia cells. Sequencing of germline DNA revealed a higher frequency of MICA*00801/A5.1 in patients with large granular lymphocyte leukemia than in matched controls (64% versus 41%, P<0.001, homozygous 40% versus 15%, P<0.001). Flow cytometry was employed to determine the expression of MICA within hematologic compartments, showing that the signal intensity of MICA was increased in granulocytes from neutropenic patients with large granular lymphocyte leukemia in comparison with that in controls (P=0.033). Furthermore, neutrophil counts were inversely correlated with MICA expression (R 2 =0.50, P=0.035). Finally, large granular lymphocyte leukemia cells were able to selectively kill MICA + Ba/F3 lymphocytes transfected with human MICA*019 in a dose-dependent manner compared to naïve cells (P<0.001), an effect mitigated by administration of an anti-NKG2D antibody (P=0.033). ConclusionsOur results illustrate that MICA-NKG2D played a role in disease pathogenesis in the majority of patients in our cohort of cases of large granular lymphocyte leukemia and further investigation into this signaling axis may provide potent therapeutic targets. Haematologica 2010;95(10): 1713-1721. doi:10.3324/haematol.2010 MICA polymorphism identified by whole genome array associated with NKG2D-mediated cytotoxicity in T-cell large granular lymphocyte leukemia © F e r r a t a S t o r t i F o u n d a t i o n

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Polymorphism in MICA rather than HLA-B/C genes is associated with psoriatic arthritis in the Jewish population

Cited by 78 publications

References 26 publications

Angiotensin-converting enzyme gene polymorphism in patients with psoriatic arthritis

Angiotensin-converting enzyme gene polymorphism in patients with psoriatic arthritis

The increase of MICA gene A9 allele associated with gastric cancer and less schirrous change

MICA polymorphism identified by whole genome array associated with NKG2D-mediated cytotoxicity in T-cell large granular lymphocyte leukemia

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