Different HLA-DR-DQ and MHC class I chain-related gene A (MICA) genotypes in autoimmune and nonautoimmune gestational diabetes in a Swedish population

Törn, Carina; Gupta, Manu; Sanjeevi, Carani B.; Åberg, Anders; Frid, Anders; Landin‐Olsson, Mona

doi:10.1016/j.humimm.2004.09.002

Cited by 21 publications

(17 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HLA-DQ is non-covalently associated with DQβ, which has been associated with T1D susceptibility in multiple populations [51-54]. In contrast, few studies have associated any HLA class II genes, including HLA-DRB3 genes, induced in GDM [53]. Although a role of HLA class II genes in T1D pathogenesis has not yet been established, decreased surface expression of HLA-DQ molecules on CD4 and CD8 peripheral cells has been reported in recently diagnosed T1D patients exhibiting DQB1 susceptibility alleles.…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

et al. 2014

View full text Add to dashboard Cite

BackgroundType 1 diabetes (T1D) is an autoimmune disease, while type 2 (T2D) and gestational diabetes (GDM) are considered metabolic disturbances. In a previous study evaluating the transcript profiling of peripheral mononuclear blood cells obtained from T1D, T2D and GDM patients we showed that the gene profile of T1D patients was closer to GDM than to T2D. To understand the influence of demographical, clinical, laboratory, pathogenetic and treatment features on the diabetes transcript profiling, we performed an analysis integrating these features with the gene expression profiles of the annotated genes included in databases containing information regarding GWAS and immune cell expression signatures.MethodsSamples from 56 (19 T1D, 20 T2D, and 17 GDM) patients were hybridized to whole genome one-color Agilent 4x44k microarrays. Non-informative genes were filtered by partitioning, and differentially expressed genes were obtained by rank product analysis. Functional analyses were carried out using the DAVID database, and module maps were constructed using the Genomica tool.ResultsThe functional analyses were able to discriminate between T1D and GDM patients based on genes involved in inflammation. Module maps of differentially expressed genes revealed that modulated genes: i) exhibited transcription profiles typical of macrophage and dendritic cells; ii) had been previously associated with diabetic complications by association and by meta-analysis studies, and iii) were influenced by disease duration, obesity, number of gestations, glucose serum levels and the use of medications, such as metformin.ConclusionThis is the first module map study to show the influence of epidemiological, clinical, laboratory, immunopathogenic and treatment features on the transcription profiles of T1D, T2D and GDM patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

et al. 2014

View full text Add to dashboard Cite

show abstract

“…A higher frequency of the type 1 diabetes high-risk HLA genotypes was observed in patients with GDM, but only in those women that were found to be positive for islet autoantibody at delivery [9]. When the GDM population was classified according to the presence or absence of islet cell autoantibodies, a higher frequency of HLA-DR3/DR4 in the autoimmune group and of HLA-DR7-DQ2/γ, -DR9-DQ9/γ and -DR14-DQ5/γ were observed in the non-autoimmune group [10]. In our study, we excluded antibody-positive women with GDM and antibody-positive control mothers in order to exclude women who would be considered at risk of developing type 1 diabetes in the future.…”

Section: Discussionmentioning

confidence: 99%

The type 1 diabetes protective HLA DQB1*0602 allele is less frequent in gestational diabetes mellitus

et al. 2009

View full text Add to dashboard Cite

Aims/hypothesis We tested whether gestational diabetes mellitus (GDM) is associated with HLA-DQ genotypes. Methods A total of 764 mothers with non-autoimmune (GAD65, insulinoma-associated protein 2 [IA-2] and insulin autoantibody-negative) GDM were ascertained between September 2000 and August 2004 in the population-based Diabetes Prediction in Skåne (DiPiS) study. HLA-DQB1 genotypes were determined in these mothers and in 1191 randomly selected non-diabetic control mothers also negative for islet autoantibodies. The data were analysed in relation to maternal age, country of birth, number of pregnancies/ siblings and pregnancy weight gain. Results The frequency of type 1 diabetes high-risk HLA-DQ alleles (DQB1*0201, DQB1*0302) did not differ between GDM mothers and controls. In contrast, the low-risk DQB1*0602 allele was less prevalent (OR 0.64, 95% CI= 0.51-0.80, p=0.0006) in GDM than in control mothers. The difference in DQB1*0602 frequency between GDM mothers and controls remained after multiple logistic regression analysis correcting for maternal age, country of birth, number of pregnancies/siblings and weight gain during pregnancy (OR 0.67, 95% CI 0.51-0.88, p=0.009). Conclusions/interpretation The negative association between mothers who have non-autoimmune GDM and HLA-DQ*0602 suggest that this allele may protect not only from type 1 diabetes but also from GDM.

show abstract

“…In addition, in GDM women with GAD65Ab, the frequencies of DR4 and DQB1*0302 alleles were significantly higher than in controls [84]. It has been shown that women with GDM who were positive for at least one antibody (ICA, GAD65Ab or IA-2A) had significantly higher frequency of HLA DR3-DQ2/X or DR4-DQ8/X compared to healthy control subjects from Sweden [85]. Moreover, women with GDM who were negative for those antibodies had an increased frequency of HLA DR7-DQ2/X, DR9-DQ9/X and DR14-DQ5/X compared to controls [85].…”

Section: Human Leukocyte Antigen (Hla)mentioning

confidence: 98%

“…It has been shown that women with GDM who were positive for at least one antibody (ICA, GAD65Ab or IA-2A) had significantly higher frequency of HLA DR3-DQ2/X or DR4-DQ8/X compared to healthy control subjects from Sweden [85]. Moreover, women with GDM who were negative for those antibodies had an increased frequency of HLA DR7-DQ2/X, DR9-DQ9/X and DR14-DQ5/X compared to controls [85]. We have also demonstrated that HLA DQB1 risk genotypes [i.e.…”

Section: Human Leukocyte Antigen (Hla)mentioning

confidence: 99%

Genetics of Gestational Diabetes Mellitus

Shaat¹,

Groop

2007

CMC

View full text Add to dashboard Cite

About 2-5% of all pregnant women develop gestational diabetes mellitus (GDM) during their pregnancies and the prevalence has increased considerably during the last decade. GDM is a heterogeneous disorder that is defined as carbohydrate intolerance with onset or first recognition during pregnancy. It is manifested when pancreatic beta cells are no longer able to compensate for the increased insulin resistance during pregnancy, but the pathogenesis of the disease is still largely unknown. GDM is considered to result from interaction between genetic and environmental risk factors. Genetic predisposition to GDM has been suggested since GDM clusters in families. Also, women with mutations in MODY (Maturity onset diabetes of the young) genes often present with GDM. In addition, common variants in several candidate genes (e.g. potassium inwardly rectifying channel subfamily J, member 11 [KCNJ11], Glucokinase [GCK], Hepatocyte nuclear factor-1alpha [HNF1A] etc.) have been demonstrated to increase the risk of GDM. Old age, obesity and high fat diet represent some important non-genetic factors. There are several approaches to search for genes predisposing to a polygenic disease like GDM including linkage and association studies, expression profiling and animal models. A combination of several methods is usually necessary. Identification of the underlying genetic causes of GDM will eventually give a better view of the mechanisms that contribute to the pathophysiology of the disease. Furthermore, it may improve options to possibly prevent GDM and complications for the mother and her child. This review focuses on the genetics of GDM and possible implications in clinical practice.

show abstract

Different HLA-DR-DQ and MHC class I chain-related gene A (MICA) genotypes in autoimmune and nonautoimmune gestational diabetes in a Swedish population

Cited by 21 publications

References 44 publications

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation

The type 1 diabetes protective HLA DQB1*0602 allele is less frequent in gestational diabetes mellitus

Genetics of Gestational Diabetes Mellitus

Contact Info

Product

Resources

About