Table 1.
List of Genetic loci in Metabolic Syndrome Pathway
| Category | Gene Name | Chromosome | Entrez Gene ID | Role |
|---|---|---|---|---|
| Hypothalamic Genes | FTO† | 16q12.2 | 79068 | Severe obesity/insulin resistance |
| MC4R† | 18q21.32 | 4160 | Member of G-protein coupled receptor family, signaling hormone involved in energy homoeostasis | |
| PPARG† | 3p25.2 | 5468 | Transcription factor involved in adipogenesis and type 2 diabetes risk | |
| ADIPOQ | 3q27.3 | 9370 | Adipose tissue specific protein involved in insulin sensitizing and anti-atherosclerotic properties | |
| LEPTIN | 7q31.3 | 3952 | Signaling hormone affects directly or indirectly on the central nervous system to inhibit food intake and/or regulate energy expenditure as part of a homeostatic mechanism | |
| Hepatic Genes | ||||
| Dyslipidemia | APOE-CI-CII-CIV† | 19q13.32 | 2282 | Cluster of triglyceride-rich lipoprotein receptor ligands for LDL receptor –related proteins |
| APOB† | 2p24.1 | 338 | Main apolipoprotein of chylomicrons and low density lipoproteins, functions as a recognition signal for the cellular binding and internalization of LDL particles | |
| APOAV-AIV-CIII-AI† | 11q23.3 | 117536 | Cluster of apolipoproteins plays an important role in regulating the plasma triglyceride levels | |
| GALNT2 | 1q42.13 | 2590 | Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis | |
| PCSK9 | 1p32.3 | 255738 | Decreases plasma cholesterol and LDL cholesterol and provides protection from coronary artery disease | |
| CETP† | 16q13 | 1071 | Exchanges cholesterol esters for triglycerides from HDL and triglyceride rich lipoproteins | |
| LCAT† | 16q22.1 | 3931 | Required for remodeling HDL particles into their spherical forms | |
| ABCA1† | 2p23.3 | 2646 | Functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in this gene cause Tangier’ disease and familial HDL deficiency. | |
| LPL† | 8p21.3 | 4023 | Catalyzes the hydrolysis of triglycerides to release free fatty acids into the circulation | |
| LIPC† | 15q21.3 | 3990 | Encodes hepatic triglyceride lipase in liver and hydrolyses triglycerides | |
| ANGPTL4† | 19p13.2 | 51129 | Plasma hormone directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity and also acts as an apoptosis factor for vascular endothelial cells | |
| NAFLD | MTTP | 4q23 | 4547 | Catalyzes the transport of triglyceride, cholesterol ester, and phospholipid between phospholipid surfaces |
| ENPP1 | 6q23.2 | 5167 | Involved primarily in ATP hydrolysis at the plasma membrane. Appears to modulate insulin sensitivity | |
| APOCIII† | 11q23.3 | 345 | Inhibits lipoprotein lipase; it delays catabolism of triglyceride-rich particles, induces the development of hypertriglyceridemia | |
| PNPLA3† | 22q13.31 | 80339 | Triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes | |
| Hypertension | WNK1 | 12p13.33 | 65125 | A key regulator of blood pressure by controlling the transport of sodium and chloride ions |
| KCNJ1 | 11q24.3 | 3758 | Mutations in this gene have been associated with Bartter syndrome, which is characterized by salt wasting, hypercalciuria, and low blood pressure | |
| NPR3 | 5p13.3 | 4883 | Encodes natriuretic peptides which regulate blood volume and pressure, pulmonary hypertension, and cardiac function | |
| GUCY1A3 | 4q32.1 | 2982 | guanylyl cyclases are groups of enzymes that mediate important communication between the heart, intestine and kidney to regulate blood volume and Na+ balance. | |
| GNAS | 20q13.32 | 4686 | Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems | |
| NPPA-NPPB | 1q36.22 | 9757 | Natriuretic peptide receptors are associated with intracellular guanylyl cyclase activity and involved in homeostasis of body fluid volume | |
| CYP17A1† | 10q24.32 | 1586 | Mono-oxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and lipids; gene variants associated with hypertension | |
| C21orf91† | 21q21.1 | 54149 | Gene variants associated with systolic blood pressure | |
| GPR98† | 5q14.3 | 84059 | Associated with Usher syndrome 2 and familial febrile seizures, gene variants associated with diastolic blood pressure | |
| ARRDC3 | 5q14.3 | 57561 | Gene variants associated with diastolic blood pressure | |
| β-cell function, insulin secretion and insulin resistance, and type 2 diabetes genes | GCKR† | 2p23.3 | 2646 | Enzyme regulators, controls activity of glucokinase in liver and brain |
| G6PC2† | 2q24.3 | 57818 | Enzyme, transport channel, key role in glucose homeostasis | |
| CDKN2A-B† | 9p21.3 | 1029 | Enzyme, anti-oncogene involved in pancreatic carcinomas, type 2 diabetes | |
| GLUT4 | 17 p13.1 | 6517 | Solute carrier family 2, mediates insulin-stimulation glucose uptake in adipocytes & muscles | |
| INSR | 19 p13.3 | 3643 | Signaling hormone receptor tyrosine kinase | |
| HNF4A† | 20q12 | 3172 | Transcription factor regulates genes required for glucose transport and metabolism | |
| ADAM 30† | 1p12-p11 | 11085 | Disintegrin and metalloproteinase domain-containing protein 30 has been implicated in a variety of biological processes and associated with type 2 diabetes risk | |
| NOTCH2† | 1p13-p11 | 4853 | Transcription regulator, type 2 diabetes | |
| THADA† | 2p21 | 63892 | Death receptor membrane protein, gene variants associated with type 2 diabetes | |
| ADAMTS9† | 3p14.3 | 56999 | Enzyme, anti-oncogene, associated with type 2 diabetes | |
| JAZF1† | 7p15.2 | 221895 | Transcription factor, increases risk for prostate cancer, type 2 diabetes | |
| TSPAN8† | 12q14.1 | 7103 | Regulatory protein involved in cell development, growth and motility, type 2 diabetes | |
| IGF2BP2† | 3q27.2 | 10644 | Regulatory enzyme influences insulin secretion | |
| CDKAL1† | 6p22.2 | 54901 | Variant confers risk through reduced insulin secretion | |
| GCK† | 7p14 | 2645 | Modulates insulin secretion, glucolysis, energy pathways | |
| SLC30A8† | 8q24.11 | 169026 | Facilitates transportation of zinc from cytoplasm into insulin containing vesicles | |
| TCF7L2† | 10 q25.2 | 6934 | Transcription regulator influences insulin secretion | |
| INS | 11 p15.5 | 3630 | Signaling hormone, increases cell permeability to monosaccharides, amino acids and fatty acids | |
| CDC123† | 10p13 | 8872 | Involved in transcription regulation, insulin secretion | |
| HHEX | 10q23.33 | 3087 | Transcription factor involved in hematopoietic differentiation, pancreatic development, insulin secretion | |
| KCNJ11† | 11 p15.1 | 3767 | Ion channel transporter | |
†
Gene association detected in GWAS