The relationships between HLA class II alleles and antigens with gestational diabetes mellitus: A meta-analysis

Abstract

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy. It is associated with an increased risk of pregnancy complications. Susceptibility to GDM is partly determined by genetics and linked with type 1 diabetes-associated high risk HLA class II genes. However, the evidence for this relationship is still highly controversial. In this study, we assessed the relationship between HLA class II variants and GDM. We performed meta-analysis on all of literatures available in PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases. The odds ratio and 95% confidence interval of each variant were estimated. All statistical analyses were conducted using the Comprehensive Meta Analysis 2.2.064 software. At the allelic analysis, DQB1*02, DQB1*0203, DQB1*0402, DQB1*0602, DRB1*03, DRB1*0301 and DRB1*1302 reached a nominal level of significance, and only DQB1*02, DQB1*0602 and DRB1*1302 were statistically significant after Bonferroni correction. At the serological analysis, none of DQ2, DQ6, DR13 and DR17 was statistically significant following Bonferroni correction although they reached a nominal level of significance. In sum, our meta-analysis demonstrated that there were the associations between HLA class II variants and GDM but more studies are required to elucidate how these variants contribute to GDM susceptibility.Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy 1 . The manifestation of GDM is reportedly influenced by age 2 , ethnicity 3 , BMI 4 , and family history of GDM of the pregnant woman 5 . Despite all this information, the pathogenesis of GDM still remains obscure. Since GDM is regarded as a risk factor for developing type 2 diabetes 6 , many investigators have mainly focused on the linkage between GDM and type 2 diabetes. However, Lapolla et al. 7 reported that presentation of pancreatic islet autoantibodies during GDM is predictive for type 1 diabetes development. A number of studies have demonstrated that the circulating immune markers of type 1 diabetes (such as anti-islet cell antibodies and anti-GAD antibodies) are present in the blood of pregnant women with GDM [8][9][10][11] . There is no doubt that we could understand the pathology underlying GDM better, if more genetic risk variants that are shared by type 1 diabetes and GDM were identified. The major type 1 diabetes susceptibility variants are HLA class II genes located on chromosome 6p21, which account for up to 30-50% of the heritability of type

Identification of hub‐methylated differentially expressed genes in patients with gestational diabetes mellitus by multi‐omic WGCNA basing epigenome‐wide and transcriptome‐wide profiling

“…Several immune‐related genes were hypermethylated and dysregulated expressed in visceral omental adipose tissue in the GDM group compared with controls . Furthermore, downregulation of both MHC class I genes and MHC class II genes were found in GDM, and GDM susceptibility is known to be associated with HLA class II genes in type 1 diabetes . However, further studies are needed to explain how HLA‐F contributes to GDM pathogenesis.…”

Identification of potential gene markers in gestational diabetes mellitus

“…HLA‐DPA1 , another under‐expressed gene, has been reported to signally enhance the risk of developing T1DM. Interestingly, Guo et al performed a meta‐analysis of GDM risk and HLA class II mutations ( DQB1 and DRB1 ), finding that DQB1 *02 and DRB1 *1302 were related to elevated risks for progression to GDM 26 . Therefore, it can be inferred that four HLA class II variants ( HLA‐DQA1 , HLA‐DRB1 , HLA‐DPA1, and HLA‐DQB1 ) were probably involved in the molecular mechanisms of GDM progression.…”

Identification of diagnostic biomarker in patients with gestational diabetes mellitus based on transcriptome‐wide gene expression and pattern recognition

“…28 However, there are growing evidence suggesting that GDM is also associated with type I diabetes, which is a chronic autoimmune disease concerned with the immunemediated injury of pancreatic β-cells and the compromised endogenous insulin production. 29,30 Therefore, identification of more molecular biomarkers that are shared by GDM and both types of diabetes will be helpful for understanding as well as diagnosing GDM. In this study, we found that the key players in the regulatory network of DEG profiles were products encoded by the HLA class II genes, which are responsible for producing self-antigens and regulating autoimmunity.…”

“…GDM was originally regarded as a risk factor for developing type II diabetes . However, there are growing evidence suggesting that GDM is also associated with type I diabetes, which is a chronic autoimmune disease concerned with the immune‐mediated injury of pancreatic β‐cells and the compromised endogenous insulin production . Therefore, identification of more molecular biomarkers that are shared by GDM and both types of diabetes will be helpful for understanding as well as diagnosing GDM.…”