Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study

Kirsten, Holger; Petit-Teixeira, Élisabeth; Scholz, Markus; Hasenclever, Dirk; Hantmann, Helene; Heider, Dirk; Wagner, Ulf; Sack, Ulrich; Teixeira, Vítor Hugo; Prum, Bernard; Burkhardt, Jana; Pierlot, Céline; Emmrich, Frank; Cornélis, François; Ahnert, Peter

doi:10.1186/ar2683

Cited by 46 publications

(41 citation statements)

References 39 publications

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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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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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“…Although our data shows for the first time the involvement of the ULBP family of NKG2D ligands (NKG2DLs) in the pathogenesis of an autoimmune disease (17), other NKG2DLs have been associated with various autoimmune disorders (47). For example, specific MICA alleles are overrepresented in RA, inflammatory bowel disease and T1D patients, implicating a role in disease pathogenesis (48, 49). Likewise, MICB polymorphisms are also associated with CeD, ulcerative colitis, and MS (50–52).…”

Section: The Impact Of Genetic Studies In Aa Researchmentioning

confidence: 99%

Genetic Basis of Alopecia Areata

Jabbari

Petukhova

Cabral

et al. 2013

Dermatologic Clinics

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Synopsis Alopecia Areata (AA) is a recurrent autoimmune type of hair loss that affects about 5.3 million people in the United States alone. Despite being the most prevalent autoimmune disease, affecting more individuals than most other autoimmune diseases combined, the molecular and cellular mechanisms underlying this complex disease are still poorly understood, and rational treatments are lacking. It is currently accepted that AA is an autoimmune disease that occurs in genetically susceptible individuals and that environmental factors play a role in the development and progression of the disease. However, further efforts are necessary to clearly pinpoint the causes and molecular pathways leading to this disease and, most importantly, to find evidence-based treatments to treat AA. Here, we will focus on the central role of genetics for gaining insight into disease pathogenesis and setting the stage for the rational development of novel effective therapeutic approaches. This is an exciting new era marking the beginning of translational research in AA based on genetic findings.

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“…MICA triggers the cytolysis of virus infected or transformed cells mediated by NKG2D-bearing cells [3] and provides co-stimulatory signal for CD8 ϩ ␣␤ T-cell activation in pathogenspecific immune response [4]; MICA polymorphisms have been shown to modulate binding affinities with NKG2D receptor [5]. In addition to the role in immune surveillance, recent data highlight the importance of MICA/MICB molecules in organ transplantation [6,7] and in HLA-linked disease association [8,9].…”

Section: Introductionmentioning

confidence: 99%

MICA polymorphism in a northern Chinese Han population: The identification of a new MICA allele, MICA*059

et al. 2010

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Association of MICA with rheumatoid arthritis independent of known HLA-DRB1 risk alleles in a family-based and a case control study

Cited by 46 publications

References 39 publications

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

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

Genetic Basis of Alopecia Areata

MICA polymorphism in a northern Chinese Han population: The identification of a new MICA allele, MICA*059

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