Table 3.
Genes associated with T1D, T2D, metabolism, or obesity | ||||
---|---|---|---|---|
Gene | Description | Significance | Reference | |
CADM2 | cell adhesion molecule 2 | SNP associated with risk of obesity, regulates insulin sensitivity | Speliotes et al. (30); Dorajoo, 2012; Rathjen et al. (31); Yan, 2018 |
|
BCL2L15 | BCL2-like 15 | Gene located in a T1D-associated loci. | T1Dbase.org | |
ERAP1 | endoplasmic reticulum aminopeptidase 1 | Gene located in a T1D-associated loci. | Fung et al. (32) | |
ETV5 | ets variant 5 | SNP located near ETV5 gene linked to obesity. | Thorleifsson et al. (33) | |
KANK1 | KN motif and ankyrin repeat domains 1 | Variants associated with fasting proinsulin & insulinogenic index | Huyghe et al. (34) | |
SIM1 | single-minded family bHLH transcription factor 1 | Gene in an obesity-associated loci. | Meyre et al. (35) | |
PLXNA4 | plexin A4 | Gene associated with T2D. | Saxena et al. (36) | |
TRPM5 | transient receptor potential cation channel, subfamily M, member 5 | TRPM5 variants associated with pre-diabetic phenotypes. Regulates insulin secretion and loss of expression leads to a pre-diabetic phenotype. |
Brixel et al. (37); Ketterer et al. (38) |
|
ABCB9 | ATP-binding cassette, sub-family B, member 9 | Gene variant that confers susceptibility for T2D. | Harder et al. (39) | |
Biologically relevant to pathogenesis of T1D – Genes upregulated in AA+ | ||||
PGC | Progastricsin (pepsinogen C) | Expressed in human islets and is converted to the proteolytic enzyme pepsin in low pH. | Hassan et al. (40) | |
CEACAM6 | carcinoembryonic antigen-related cell adhesion molecule 6 | Involved in insulin homeostatsis and T cell proliferation, and serves as receptor for host-specific viruses and bacteria. | Kuespert, 2006 | |
CALB1 | calbindin 1, 28kDa | Overexpression reduces glucose-stimulated insulin secretion by modulating calcium influx. | Lee et al. (41) | |
S100B | S100 calcium binding protein B | An inflammatory protein that serves as a ligand for the receptor of advanced glycation end products that are involved in the development of pathogenic T cells and apoptosis of beta cells. | Chen et al. (42) | |
SMPD3 | sphingomyelin phosphodiesterase 3,neutral membrane | Can mediate cellular responses to IL-1b and TNFa. | Rutkute et al. (43) | |
IL33 | interleukin 33 | May promote the development of inflammatory autoimmune T cells in experimental models of T1D. | Milovanovic et al. (44) | |
ETV5 | ets variant 5 | Controls differentiation of TH17 cells. | Pham et al. (45) | |
Biologically relevant to pathogenesis of T1D—Genes downregulate in AA+ | ||||
CRH | corticotropin releasing hormone | expressed in beta cells. Plays a role in insulin secretion and beta cell proliferation. | Kanno et al. (46); Huising et al. (47) |
|
PDK4 | pyruvate dehydrogenase kinase, isozyme 4 |
A key modulator of glucose homeostasis. Regulates expression of the transcription factor Ptf1a. | Dateki et al. (48); Zhang, 2014 |
|
ANGPTL4 | angiopoietin-like 4 | Involved in glucose homeostasis, lipid metabolism, and insulin sensitivity. Regulates islet morphology. | Xu et al. (49); Kim et al. (50) |
|
SCIMP | SLP adaptor and CSK interacting membrane protein | Expressed on B cells and involved in signal transduction after MHCII stimulation. | Draber et al. (51) | |
SEZ6L | seizure related 6 homolog-like | A substrate for BACE2, an inhibitor of beta cell proliferation. | Stutzer et al. (52) | |
ICOSLG | inducible T-cell co-stimulator ligand |
Provides co-stimulation through ICOS, and may be involved in the expansion of activated Tregs | Martin-Orozco et al. (53) | |
PLD1 | phospholipase D1, phosphatidylcholine-specific | Phosphatidic acid formation on the graunule membrane by PLD1 is essential for glucose-stimulated insulin secretion | Ma et al. (54) | |
TRPM5 | transient receptor potential cation channel, subfamily M, member 5 | TRPM5 variants associated with pre-diabetic phenotypes. Regulates insulin secretion and loss of expression leads to a pre-diabetic phenotype. |
Brixel et al. (37); Ketterer et al. (38) |
|
GNLY | granulysin | An antimicrobial peptide. Reduced GNLY expression has been observed in the PBMCs of T1D patients | Jin et al. (55) | |
CRTAM | cytotoxic and regulatory T cell molecule | Involved in establishing late phase T cell polarity, and allows increased production of IFNγ and IL22. | Yeh et al. (56) | |
CD180 | CD180 molecule (RP105) |
An important modulator of Toll-like receptor 4 signaling that is involved in activating innate and adaptive immune responses. | Divanovic et al. (57) | |
FCGR2B | Fc fragment of IgG, low affinity IIb, receptor |
Impaired FCGR2B function leads to abberant B cell activation and the development of autoimmunity. Reduced Fcgr2b linked to autoimmune susceptibility in NOD mice. | Jiang et al. (26); Xiu et al. (27); Anania et al. (20) |
|
CLEC4D | C-type lectin domain family 4, member D | Plays a non-redundant role in protecting against anti-mycobacterial and fungal infection. | Wilson et al. (58) | |
IL4R | interleukin 4 receptor | IL4 can prevent autoimmune diabetes in rodent models of T1D. | Ko et al. (59) | |
RGS16 | regulator of G-protein signaling 16 | Key factor in G-protein mediated activation of lymphocytes. Plays a role in beta-cell development, proliferation, and insulin secretion. | Villasenor et al. (60); Vivot et al. (61) |