MICA is Associated with Type 1 Diabetes in the Belgian Population, Independent of HLA-DQ

Autreve, Jan E. Van; Koeleman, Bobby P. C.; Quartier, Erik; Aminkeng, Folefac; Weets, Ilse; Gorus, Frans; Auwera, Bart J. Van der; Registry, Belgian Diabetes

doi:10.1016/j.humimm.2006.02.032

Cited by 16 publications

(13 citation statements)

References 40 publications

(44 reference statements)

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“…Studies performed in different populations showed an association of different MICA alleles with type 1 diabetes (1,29,36,38). In addition, several studies demonstrated the association of MICA alleles with the age of the patient presenting the clinical onset of T1D (16,21) or an association with LADA (16,31).…”

Section: Discussionmentioning

confidence: 99%

“…The association of the HLA complex present on chromosome 6 does not alone explain the total linkage of the HLA region to T1D, leading to the hypothesis of the probable existence of additional causal genes for immune-related disorders in this region. Studies report that polymorphism on the MICA genes could be a potential candidate for association with T1D and LADA (1,17,29,35,38). In this study, we aimed to study allele polymorphism and the functionally relevant dimorphism (129 Val/Met) of the MICA gene in younger T1D and LADA patients in the Algerian population.…”

mentioning

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: Discussionmentioning

confidence: 99%

mentioning

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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“…Many (7)(8)(9)11). This subgrouping causes a multiple testing problem and reduces the sample set and hence the power to detect MHC class II-independent effects.…”

Section: Discussionmentioning

confidence: 99%

Sequencing-Based Genotyping and Association Analysis of the MICA and MICB Genes in Type 1 Diabetes

et al. 2008

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OBJECTIVE-The nonclassical major histocompatibility complex (MHC) class I chain-related molecules (MICs), encoded within the MHC, function in immunity. The transmembrane polymorphism in MICA (MICA-STR) has been reported to be associated with type 1 diabetes. In this study, we directly sequenced both of the highly polymorphic MIC genes (MICA and MICB) in order to establish whether they are associated with type 1 diabetes independently of the known type 1 diabetes MHC class II genes HLA-DRB1 and HLA-DQB1. RESEARCH DESIGN AND METHODS-We developed a sequencing-based typing method and genotyped MICA and MICB in 818 families (2,944 individuals) with type 1 diabetes from the U.K. and U.S. (constructing the genotype from single nucleotide polymorphisms in exons 2-4 of MICA and 2-5 of MICB) and additionally genotyped the MICA-STR in 2,023 type 1 diabetic case subjects and 1,748 control subjects from the U.K. We analyzed the association of the MICA and MICB alleles and genotypes with type 1 diabetes using regression methods.RESULTS-We identified known MICA and MICB alleles and discovered four new MICB alleles. Based on this large-scale and detailed genotype data, we found no evidence for association of MICA and MICB with type 1 diabetes independently of the MHC class II genes (MICA P ϭ 0.08, MICA-STR P ϭ 0.76, MICB P ϭ 0.03, after conditioning on HLA-DRB1 and HLA-DQB1). A pproximately 50% of the familial clustering of type 1 diabetes is attributable to the major histocompatibility complex (MHC) region on human chromosome 6p21, and the MHC class II genes HLA-DRB1 and HLA-DQB1 account for a large proportion of this clustering (1). However, association studies in the MHC region indicate that other genes have effects in type 1 diabetes independently of the class II genes (2-4). Identification of these genes is complicated because genes in the MHC have multiple alleles and exhibit extensive linkage disequilibrium (LD), and the class II genes HLA-DQB1 and HLA-DRB1 show complicated dominance and epistatic effects. Importantly, any putative new effect must be distinguished from the effect of these class II genes (2,3). CONCLUSIONS-CommonThe nonclassical MHC class I chain-related molecule (MIC) genes MICA and MICB are located 46.4 and 141.2 kb, respectively, centromeric of HLA-B and ϳ2 Mb telomeric of HLA-DRB1 (5) and have been associated both with immunity and with autoimmune diseases (5). In common with most MHC HLA genes, alleles of MICA and MICB are named based on haplotypes of nonsynonymous single nucleotide polymorphisms (nsSNPs). However, the most studied polymorphism in either of these genes is a short tandem repeat (STR) in the transmembrane domain of MICA (MICA-STR). Whether these genes are associated with type 1 diabetes is uncertain, with multiple conflicting reports in the literature (3,6 -14). Most of these studies failed to demonstrate convincingly that the association is independent of the MHC class II genes, and all were restricted to analyses of the MICA-STR. The MICA-STR is a GCT repeat microsatellite in MICA ex...

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“…Adult-onset type 1 diabetes and LADA, but not childhoodonset type 1 diabetes, are also associated with the HLA class I related A gene 5.1 [23], although two recent studies did not confirm this finding [24,25]. Van Autreve et al [24] demonstrated a significant association of type 1 diabetes with MICA 5 but not with MICA 5.1, furthermore patients stratified according to the presence or absence of the different MICA alleles did not differ in terms of age at onset. In their case-control study, Alizadeh et al found that MICA 5 but not MICA 5.1 was significantly associated with an increased risk of type 1 diabetes, nevertheless the meta-analysis they reported in the same study did not show an association of type 1 diabetes either with MICA 5 or MICA 5.1 [25].…”

Section: The Periodic Table Of Lifementioning

confidence: 96%

“…[20] Strikingly, even adults with non-insulinrequiring diabetes without the diabetes-associated GADA, as well as KPD cases, from a sub-type with reduced insulin secretion and diabetes-associated autoantibodies, have an excess of diabetes-associated HLA alleles [19,21,22]. Adult-onset type 1 diabetes and LADA, but not childhoodonset type 1 diabetes, are also associated with the HLA class I related A gene 5.1 [23], although two recent studies did not confirm this finding [24,25]. Van Autreve et al [24] demonstrated a significant association of type 1 diabetes with MICA 5 but not with MICA 5.1, furthermore patients stratified according to the presence or absence of the different MICA alleles did not differ in terms of age at onset.…”

Section: The Periodic Table Of Lifementioning

confidence: 97%

Diabetes classification: grey zones, sound and smoke: Action LADA 1

Leslie

Kolb

Schloot

et al. 2008

Diabetes Metabolism Res

123

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Diseases gain identity from clinical phenotype as well as genetic and environmental aetiology. The definition of type 1 diabetes is clinically exclusive, comprising patients who are considered insulin dependent at diagnosis, whilst the definition of type 2 diabetes is inclusive, only excluding those who are initially insulin dependent. Ketosis-prone diabetes (KPD) and latent autoimmune diabetes in adults (LADA) are each exclusive forms of diabetes which are, at least initially, clinically distinct from type 2 diabetes and type 1 diabetes, and each have a different natural history from these major types of diabetes.KPD can be diagnosed unequivocally as diabetes presenting with the categorical clinical feature, ketoacidosis. In contrast, LADA can be diagnosed by the co-occurrence of three traits, not one of which is categorical or exclusive to the condition: adult-onset non-insulin-requiring diabetes, an islet autoantibody such as glutamic acid decarboxylase autoantibodies (GADA) or cytoplasmic islet cell autoantibodies (ICA), and no need for insulin treatment for several months post-diagnosis. But while some would split diabetes into distinct subtypes, there is a strong case that these subtypes form a continuum of varying severity of immune and metabolic dysfunction modified by genetic and non-genetic factors. This article discusses the nature of disease classification in general, and KPD and LADA in particular, emphasizing the potential value and pitfalls in classifying diabetes and suggesting a need for more research in this area.

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MICA is Associated with Type 1 Diabetes in the Belgian Population, Independent of HLA-DQ

Cited by 16 publications

References 40 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

Sequencing-Based Genotyping and Association Analysis of the MICA and MICB Genes in Type 1 Diabetes

Diabetes classification: grey zones, sound and smoke: Action LADA 1

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