Association analysis of MICA gene polymorphism and MICA-129 dimorphism with inflammatory bowel disease susceptibility in a Spanish population

López-Hernández, Ruth; Valdés, Mariano; Lucas, Daniel A.; Campillo, José A.; Martínez-García, Pedro J.; Salama, Hortensia; López, María Dolores; Salgado, Gema; Botella, Carmen; Minguela, Alfredo; Miras, M.; Álvarez-López, María R.; Carballo, Fernando; Muro, Manuel

doi:10.1016/j.humimm.2010.02.003

Cited by 50 publications

(53 citation statements)

References 26 publications

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“…These clinical and autoimmune markers do vary in the different age categories, supporting the conclusion that MICA contributes to the disease irrespective of the autoimmune markers and residual ␤ cell function. These findings and interpretations were in line with other pathological contexts (3,9,14,23,25,29,34,41).…”

Section: Discussionsupporting

confidence: 90%

“…In addition, MICA alleles may also be associated with susceptibility or resistance to developing autoimmunity (10). Recently, several authors have shown that the MICA-129 polymorphism was associated with several pathologies (9,14,23). In contrast, it has been demonstrated that a change of methionine to valine at position 129 of the ␣2-heavy chain domain classifies MICA alleles into strong (MICA-129 Met) or weak (MICA-129 Val) binders of NKG2D receptor (33).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Association of Major Histocompatibility Complex Class 1 Chain-Related Gene A Dimorphism with Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Algerian Population

Raache

Belanteur

Amroun

et al. 2012

Clin Vaccine Immunol

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Association of Major Histocompatibility Complex Class 1 Chain-Related Gene A Dimorphism with Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Algerian Population

Raache

Belanteur

Amroun

et al. 2012

Clin Vaccine Immunol

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“…As the Th2 response is predominant in pathological UC mucosa [49], the protective role of MICA*A4 makes sense. L opez-Hern andez and colleagues [37] described the protective role of the MICA-129Met/Val heterozygous genotype, but there were only 29 UC patients in their study and these results must be interpreted with caution. MICA*A4 is also in strong LD, with the amino acid substitution of glycine (Gly) by tryptophan (Trp) at position 14 in the a1 domain, and this change may affect the affinity of MICA with the NKG2D receptor [50].…”

Section: Discussionmentioning

confidence: 90%

“…Certain MICA-STR alleles have been associated with immune-mediated diseases [12,[25][26][27][28][29][30], including IBD: some revealed an association of MICA*A6 [31,32] or MICA*A5.1 with UC [33,34], while these results could not be replicated in other cohorts [35][36][37]. Moreover, MICA-STR alleles have been associated with UC phenotype, as location of disease [32,38], age at onset [32,39] or extraintestinal manifestations (EIMs) [7,33,39].…”

Section: Introductionmentioning

confidence: 99%

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MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset

Martínez-Chamorro

Moreno

Gómez‐García

et al. 2016

Clinical and Experimental Immunology

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SummaryUlcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chainrelated gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P 5 0Á003; OR 5 0Á643), and this protective role is higher when it forms haplotype with B*27 (P 5 0Á002; OR 5 0Á294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P 5 0Á001; odds ratio (OR) 5 2Á914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P 5 0Á002; OR 5 3Á096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P 5 0Á007; OR 5 0Á633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found.

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The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding of the NKG2D ligand MICA

et al. 2015

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The MHC class I chain-related molecule A (MICA) is a ligand for the activating natural killer (NK) cell receptor NKG2D. A polymorphism causing a valine to methionine exchange at position 129 affects binding to NKG2D, cytotoxicity, interferon-γ release by NK cells and activation of CD8+ T cells. It is known that tumors can escape NKG2D-mediated immune surveillance by proteolytic shedding of MICA. Therefore, we investigated whether this polymorphism affects plasma membrane expression (pmMICA) and shedding of MICA. Expression of pmMICA was higher in a panel of tumor (n = 16, P = 0.0699) and melanoma cell lines (n = 13, P = 0.0429) carrying the MICA-129Val/Val genotype. MICA-129Val homozygous melanoma cell lines released more soluble MICA (sMICA) by shedding (P = 0.0015). MICA-129Met or MICA-129Val isoforms differing only in this amino acid were expressed in the MICA-negative melanoma cell line Malme, and clones with similar pmMICA expression intensity were selected. The MICA-129Met clones released more sMICA (P = 0.0006), and a higher proportion of the MICA-129Met than the MICA-129Val variant was retained in intracellular compartments (P = 0.0199). The MICA-129Met clones also expressed more MICA messenger RNA (P = 0.0047). The latter phenotype was also observed in mouse L cells transfected with the MICA expression constructs (P = 0.0212). In conclusion, the MICA-129Met/Val dimorphism affects the expression density of MICA on the plasma membrane. More of the MICA-129Met variants were retained intracellularly. If expressed at the cell surface, the MICA-129Met isoform was more susceptible to shedding. Both processes appear to limit the cell surface expression of MICA-129Met variants that have a high binding avidity to NKG2D.

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Association analysis of MICA gene polymorphism and MICA-129 dimorphism with inflammatory bowel disease susceptibility in a Spanish population

Cited by 50 publications

References 26 publications

Association of Major Histocompatibility Complex Class 1 Chain-Related Gene A Dimorphism with Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Algerian Population

Association of Major Histocompatibility Complex Class 1 Chain-Related Gene A Dimorphism with Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Algerian Population

MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset

The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding of the NKG2D ligand MICA

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Association analysis of MICA gene polymorphism and MICA-129 dimorphism with inflammatory bowel disease susceptibility in a Spanish population

Cited by 50 publications

References 26 publications

Association of Major Histocompatibility Complex Class 1 Chain-Related Gene A Dimorphism with Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Algerian Population

Association of Major Histocompatibility Complex Class 1 Chain-Related Gene A Dimorphism with Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Algerian Population

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset

The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding of the NKG2D ligand MICA

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MICAA4 protects against ulcerative colitis, whereas MICAA5.1 is associated with abscess formation and age of onset