MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility

Lopez-Arbesu, Ruben; Ballina-García, Francisco Javier; Alperi-López, Mercedes; López‐Soto, Alejandro; Rodríguez-Rodero, Sandra; Martínez‐Borra, Jesús; López-Vázquez, Antonio; Fernández-Morera, Juan Luís; Riestra-Noriega, J. L.; Queiró, Rubén; Quiñones-Lombraña, Adolfo; López‐Larrea, Carlos; González, Segundo

doi:10.1093/rheumatology/kel331

Cited by 38 publications

(34 citation statements)

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“…This allele shows a reduced transcriptional activity and it is associated with less aggressive forms of celiac disease. Furthermore, we have recently described the association of MICB*004 allele to rheumatoid arthritis [70]. Now, the data presented here provide the molecular basis for the association of the MICB gene to these autoimmune diseases and they suggest that MICB may be an important candidate to become a susceptibility gene in such diseases.…”

Section: Discussionmentioning

confidence: 56%

Transcriptional regulation of MICA and MICB: A novel polymorphism in MICB promoter alters transcriptional regulation by Sp1

et al. 2007

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MHC class I-related genes A/B (MICA/B) are ligands of the NKG2D receptor expressed on T and NK cells. Their expression is highly restricted in normal tissues, but is upregulated in tumoral and infected cells. We show that the minimal promoter of both genes contains a CCAAT box, which binds to NF-Y, and a GC box, which binds to Sp1, Sp3 and Sp4. We also demonstrate that MICB promoter is polymorphic, showing three single nucleotide polymorphisms (C>G at +16, -341, -408) and a deletion of two base pairs at -66 (AG>-) that is located close to the CCAAT box (-70) and the GC box (-86). Transcriptional activity associated with MICB promoter variants carrying this deletion, present in the 45.3% of Spanish population, showed a remarkable decrease (18-fold, p <0.01). By functional analysis, we show that the deletion plays a critical role in MICB promoter activity by diminishing Sp1 transcriptional activation. These important variations in MICB expression among normal individuals could imply a significant difference in the natural immune response against infections or tumor transformation, and might thereby contribute to an increased aberrant immune response against self cells, providing the molecular basis for the associations of the MICB gene to different autoimmune diseases.

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Section: Discussionmentioning

confidence: 56%

Transcriptional regulation of MICA and MICB: A novel polymorphism in MICB promoter alters transcriptional regulation by Sp1

et al. 2007

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“…As a result there is the possibility that alleles which are specific to Asian populations within HLA-DRB1 or other loci might have been missed. Such independent RA risk contributions at non-HLA genes have been frequently suggested, such as TNF, MICA and MICB genes (26)(27)(28). To investigate the role of such non-HLA gene variants as well as other classical genes such as HLA-DQ (29), future studies incorporating larger number of individuals from multiple ethnicities would be desirable.…”

Section: Discussionmentioning

confidence: 99%

Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations

Okada

Kim

Han

et al. 2014

Human Molecular Genetics

143

164

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Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRb1 at amino acid position 13, located outside the classical shared epitope (P omnibus 5 6.9 3 10 2135 ). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr Gly > Ser)-but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional P omnibus 5 2.2 3 10 233) and 74 (conditional P omnibus 5 1.1 3 10 28). Outside of HLA-DRb1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P 5 3.8 3 10 26) and HLA-DPb1 (Phe9, conditional P 5 3.0 3 10 25 ) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino † These authors jointly directed this project.

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“…However, numerous high polymorphisms are more likely within the extracellular domain encoding exons 2, 3, and 4 of MICB. Recently, MICA and MICB gene polymorphisms have been found associated with autoimmune diseases [10] including insulin-dependent diabetes mellitus [11], Addison's disease [12, 13], celiac disease [14, 15], rheumatoid arthritis [16, 17], Behcet's disease [18, 19], and IBD [20–23], although little is known about the association between exons 2, 3, and 4 of MICB gene polymorphisms and UC.…”

Section: Introductionmentioning

confidence: 99%

MICB0106 gene polymorphism is associated with ulcerative colitis in central China

Xia

Lü

et al. 2009

Int J Colorectal Dis

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BackgroundThe highly polymorphic nonclassical MHC class I chain-related genes A and B (MICA and MICB) encode stress-inducible glycoproteins expressed on various epithelial cells including intestinal epithelial cells. MICA and MICB gene polymorphisms and expressions are associated with autoimmune diseases but not known in ulcerative colitis (UC).AimsTo investigate the association of MICB exon 2-4 polymorphisms and soluble MICA (sMICA) expression with the susceptibility of UC in central China.Materials and methodsGenomic DNA was isolated from peripheral blood. The allele frequencies of MICB exon 2-4 were genotyped in 105 UC patients and 213 healthy controls by PCR single-stranded conformation polymorphism method. Thirty-two patients and 32 controls were selected for determining serum sMICA expression by ELISA.ResultsAllele frequency of MICB0106 was significantly higher in UC patients than in healthy controls (19.0% vs. 8.9%, corrected P (Pc) = 0.0006), especially in patients with extensive colitis (24.4% vs. 8.9%, Pc = 0.0006), moderate and severe disease (24.1% vs. 8.9%, Pc = 0.0006), extraintestinal manifestations (20.5% vs. 8.9%, Pc = 0.012), male patients (22.1% vs. 8.0%, Pc = 0.006), and patients over the age of 40 years (28.8% vs. 8.3%, Pc = 0.0006). The sMICA level was significantly higher in UC than in healthy controls (604.41 ± 480.43 pg/ml vs. 175.37 ± 28.31 pg/ml, P = 0.0001) but not associated with the MICB0106 genotypes.ConclusionsOverall, MICB0106 allele was positively associated with UC in the Han Chinese in central China. sMICA was highly expressed in UC but not associated with the MICB0106 genotype.

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MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility

Cited by 38 publications

References 36 publications

Transcriptional regulation of MICA and MICB: A novel polymorphism in MICB promoter alters transcriptional regulation by Sp1

Transcriptional regulation of MICA and MICB: A novel polymorphism in MICB promoter alters transcriptional regulation by Sp1

Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations

MICB0106 gene polymorphism is associated with ulcerative colitis in central China

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