Table 2.
Major Genes That Confer Risk for Diabetes in Youth.
| Gene | Full gene name | Gene location | Diabetes association | Proposed/known diabetes-related mechanism of action |
|---|---|---|---|---|
| ABCC8 (aka SUR1) | ATP-binding cassette, subfamily C (CFTR/MRP), member 8 | 11p15.1 | PNDM, TNDM, T2D | Modulator of potassium channels and insulin release |
| FOXP3 | Forkhead box P3 | Xp11.23 | PNDM | Regulator of transcription (forkhead/winged family) |
| GCK (aka MODY2) | Glucokinase | 7p15.3–15.1 | MODY2, PNDM | Produces glucose-6-phosphate (usually first step in glucose metabolism pathway) |
| GLIS3 | GLIS family zinc finger 3 | 9p24.2 | PNDM | Activator and repressor of transcription; involved in development of pancreatic β cells |
| HLA-DQB1 (aka HLA-DQ8) | Major histocompatibility complex, Class II, DQ β 1 | 6p21.3 | T1D | Determines extracellular peptide-binding specificities on antigen-presenting cells |
| HLA-DRB3 (aka HLA-DR3) | Major histocompatibility complex, Class II, DR β 3 | 6p21.3 | T1D | Determines extracellular peptide-binding specificities on antigen-presenting cells |
| HLA-DRB4 | Major histocompatibility complex, Class II, DR β 4 | 6p21.3 | T1D | Determines extracellular peptide-binding specificities on antigen-presenting cells |
| HNF1A (aka MODY3) | HNF1 homeobox A | 12q24.2 | MODY3 | Transcription factor involved in liverspecific gene expression |
| HNF1B (aka MODY5) | HNF1 homeobox B | 17cen-q21.3 | MODY5 | Regulates development of embryonic pancreas |
| HNF4A (aka MODY1) | Hepatocyte nuclear factor 4 | 20q13.12 | MODY1 | Controls gene expression in liver; may play a role in liver development |
| HYMAI | Hydatidiform mole associated and imprinted | 6q24.3 | TNDM | Nonprotein coding, causative of TNDM; expressed only from paternal allele |
| IL2RA | Interleukin 2 receptor, α | 10p15-p14 | T1D | Encodes IL2 membrane protein; expression essential in T-cell suppression |
| INS | Insulin | 11p15.5 | PNDM, T1D | Binds to insulin receptor to stimulate uptake of glucose |
| KCNJ11 (aka Kir6.2) | Potassium inwardly rectifying channel, subfamily J, member 11 | 11p15.1 | PNDM, TNDM, T2D | Regulates potassium flow into cells; associated with the sulfonylurea receptor (SUR) |
| NEUROD1 (aka MODY6) | Neurogenic differentiation 1 | 2q32 | MODY6, T2D | Regulates expression of INS gene |
| PDX1 (aka IPF1, MODY4) | Pancreatic and duodenal homeobox 1 | 13q12.1 | MODY4, PNDM | Activates INS, GCK genes; involved in pancreatic development; involved in glucose-dependent regulation of INS gene |
| PLAGL1 (aka ZAC) | Pleiomorphic adenoma gene-like 1 | 6q24 | TNDM | Encodes C2H2 zinc finger protein involved in transactivation and DNA binding; overexpression in fetal development leads to TNDM; preferential expression of paternal allele |
| PTPN22 | Protein tyrosine phosphatase, nonreceptor type 22 (lymphoid) | 1p13.2 | T1D | May be involved in regulating protein function in T-cell receptor pathway |
| TCF7L2 | Transcription factor 7-like 2 | 10q25.3 | T2D | Involved in blood glucose homeostasis |
Note. DNA = deoxyribonucleic acid; IL2 = interleukin 2; MODY maturity-onset diabetes in the young; PNDM = permanent neonatal diabetes mellitus; T1D = type 1 diabetes; T2D = type 2 diabetes; TNDM = transient neonatal Information, 2011; Ounissi-Benkalha & Polychronakos, 2008).