HLA-DRB1 genes and the expression dynamics of HLA CIITA determine the susceptibility to T2DM

Chinniah, Rathika; Sevak, Vandit; Pandi, Sasiharan; Ravi, Padma Malini; Vijayan, Murali; Arun, K; Balakrishnan, K.

doi:10.1007/s00251-021-01212-x

Cited by 7 publications

(5 citation statements)

References 119 publications

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“…In other study made on south Indians the HLA-A alleles were also found, but this time not just on a positive significant way, it was found that allele A*68 (A*68:01:01:01), A*03 (A*03:01:01:01) and A*11 (A*11:01:01:01) showed a significant negative association which may indicate a protective function [31]. In concordance to the previously, on a Mexican American study some HLA-A and B alleles were associated to T2D on a protective way, among these ones we find the allele HLA-A2 (A*02:01:01:01), A25 (A*25:01:01:01) and A3 (A*03:01:01:01) along some B alleles like HLA-B35 [49].…”

Section: Discussionmentioning

confidence: 77%

“…The main genetic determinants of T1D are the regions of the MHC, followed by insulin gene (INS) and the protein tyrosine phosphatase non-receptor type 22 gene (PTPN22) in chromosome 6 and 11 [19][20][21]. Some authors have mentioned the association between T2D and histocompatibility antigens and most of the HLA haplotypes have been associated with a high risk to develop both, insulin and non-insulin dependent diabetes [22][23][24] and most of the reports associated with MHC-II [13][14][15][25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

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Class I MHC Polymorphisms Associated with Type 2 Diabetes in Mexican Population

Ramirez¹,

López-Olaiz²,

Morales-Fernandez³

et al. 2022

Preprint

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Type 2 diabetes has been linked to the expression of Human Leukocyte Antigens, principally to the major Histocompatibility Complex Class II and only scarce reports to Major Histocompatibility Complex class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC class I related to Type 2 diabetes in the Mexican population using the GWAS SIGMA database. This database contains information of 3,848 Mexican individuals with type 2 diabetes and 4,366 control individuals from the same population without clinical or hereditary history of the disease. The searching criteria considered a P value < 0.005 and odds ratio, OR > 1.0. Ten novel statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01), and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related with the development of Type 2 diabetes complications.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Class I MHC Polymorphisms Associated with Type 2 Diabetes in Mexican Population

Ramirez¹,

López-Olaiz²,

Morales-Fernandez³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In another study on South Indians, HLA-A alleles were also found, but this time not just in a positive significant way; it was found that alleles A*68 (A*68:01:01:01), A*03 (A*03:01:01:01), and A*11 (A*11:01:01:01) showed a significant negative association, which may indicate a protective function [31]. In accordance with previous findings, in a Mexican American study, some HLA-A and -B alleles were associated with T2D protectively; among these were the alleles HLA-A2 (A*02:01:01:01), A25 (A*25:01:01:01), and A3 (A*03:01:01:01), along with some B alleles like HLA-B35 [50].…”

Section: Discussionmentioning

confidence: 91%

“…The main genetic determinants of T1D are the regions of the MHC, followed by the insulin gene (INS) and the protein tyrosine phosphatase nonreceptor type 22 gene (PTPN22) in chromosomes 6 and 11 [19][20][21]. Some authors have mentioned the association between T2D and histocompatibility antigens, and most of the HLA haplotypes have been associated with a high risk to develop both insulin and non-insulin-dependent diabetes [22][23][24]; most reports have also associated with MHC-II [13][14][15][25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Class I MHC Polymorphisms Associated with Type 2 Diabetes in the Mexican Population

Mendoza-Ramírez

López-Olaiz

Morales-Fernández

et al. 2022

Genes

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Type 2 diabetes (T2D) has been linked to the expression of Human Leukocyte Antigens, principally to the Major Histocompatibility Complex Class II, with only scarce reports of Major Histocompatibility Complex Class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC Class I related to T2D in the Mexican population using the Genome-Wide Association Studies Slim Initiative in Genomic Medicine of the Americas (GWAS SIGMA) database. This database contains information on 3848 Mexican individuals with T2D and 4366 control individuals from the same population without a clinical or hereditary history of the disease. The searching criteria considered a p-value of <0.005 and an odds ratio (OR) of >1.0. Ten novel, statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01) and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related to the development of T2D complications.

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“…The major histocompatibility complex class II transactivator (CIITA) gene, a key regulator of MHCII, has been demonstrated to be associated with susceptibility to different autoimmune conditions such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes, T2DM, and celiac disease at the genome-wide level, [34][35][36] however, its role in the pathogenesis of periodontitis has not been investigated. In this study, we found activation of CIITA in patients with periodontitis and T2DM.…”

Section: Discussionmentioning

confidence: 99%

Decoding the role of macrophages in periodontitis and type 2 diabetes using single‐cell RNA‐sequencing

et al. 2022

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Macrophages are resident myeloid cells in the gingival tissue which control homeostasis and play a pivotal role in orchestrating the immune response in periodontitis. Cell heterogeneity and functional phenotypes of macrophage subpopulations in periodontitis remain elusive. Here, we isolated gingival tissue from periodontitis‐affected and healthy sites of patients with and without type 2 diabetes mellitus (T2DM). We then used single‐cell RNA‐sequencing (scRNA‐seq) to define the heterogeneity of tissue‐resident macrophages in gingival tissue in health vs. periodontitis. scRNA‐seq demonstrated an unforeseen gene expression heterogeneity among macrophages in periodontitis and showed transcriptional and signaling heterogeneity of identified subsets in an independent cohort of patients with periodontitis and T2DM. Our bioinformatic inferences indicated divergent expression profiles in macrophages driven by transcriptional regulators CIITA, RELA, RFX5, and RUNX2. Macrophages in periodontitis expressed both pro‐inflammatory and anti‐inflammatory markers and their polarization was not mutually exclusive. The majority of macrophages in periodontitis expressed the monocyte lineage marker CD14, indicating their bone marrow lineage. We also found high expression and activation of RELA, a subunit of the NF‐κB transcription factor complex, in gingival macrophages of periodontitis patients with T2DM. Our data suggested that heterogeneity and hyperinflammatory activation of macrophages may be relevant to the pathogenesis and outcomes of periodontitis, and may be further augmented in patients with T2DM.

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HLA-DRB1 genes and the expression dynamics of HLA CIITA determine the susceptibility to T2DM

Cited by 7 publications

References 119 publications

Class I MHC Polymorphisms Associated with Type 2 Diabetes in Mexican Population

Class I MHC Polymorphisms Associated with Type 2 Diabetes in Mexican Population

Class I MHC Polymorphisms Associated with Type 2 Diabetes in the Mexican Population

Decoding the role of macrophages in periodontitis and type 2 diabetes using single‐cell RNA‐sequencing

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