Table 2 Functional classification of major genes related to T2DM and their related morbidity
From: Genetics of type 2 diabetes mellitus in Indian and Global Population: A Review
Nos. | Gene | Major function | Disease | Population |
|---|---|---|---|---|
1 | Peroxisome proliferator-activated receptor gamma (PPARG) | Insulin resistance [53] | Central Obesity [53] Coronary heart disease [62] Acute Coronary Syndrome [61] Bladder cancer [62] | India (Delhi, Pune, Hyderabad, Punjab, Haryana, Himachal Pradesh, Delhi and Jammu and Kashmir, South Indians) [4, 24, 53] European region (Europeans, Sweden, Finland) [28, 29, 53] African region (South Africa) [40] |
2 | Potassium Inwardly Rectifying Channel Subfamily J Member 11 (KCNJ11) | Pancreatic beta-cell function [28] | Essential hypertension [63] familial persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) [64, 65] | India (Delhi, Pune, South Indians) [21, 52] UK [23] |
3 | Transcription factor 7-like 2 (TCF7L2) | Regulating glucose tolerance [28] | IGT; T2DM [55] Cardiovascular diseases [65] Type 1 diabetes mellitus [66] Gestational diabetes mellitus [66] Latent autoimmune diabetes (LADA) [66] Obesity [66] Metabolic syndrome [66] Small bowel Crohn’s disease [66] Cancer (gastric, colon, rectal, lung, breast, prostate, renal) [66] Schizophrenia [66] Bipolar disorder [66] Cystic fibrosis [66] Premature adrenarche [66] Polycystic ovarian syndrome [66] | South East Asian region–India (Delhi, Pune, Punjab, Jammu and Kashmir, Orissa, Hyderabad [21, 53, 54]) South East Asian region (Sri Lanka) [18] Europeans [53] African region (South Africa) [16] Eastern Mediterranean (Egypt) [55] American region (Mexico) [56] UK [27] |
4 | Solute carrier family 30, member 8 (SLC30A8) | Insulin packaging and secretion [53] | Breast cancer [67] Glioblastoma tumours [67] | India (Delhi, Pune); Europeans [53] Germany [19] South East Asian region (Sri Lanka) [18] |
5 | Haematopoietically expressed homeobox protein (HHEX) | Maintains beta-cell differentiation and islet function [68] | Breast cancer [69] | India (Delhi, Pune, Punjab, Jammu and Kashmir, Orissa) [53, 55] Eastern Mediterranean (Iran [59]) Western Pacific region—Korea [57] |
6 | Cyclin-dependent kinase inhibitor 2A (CDKN2A) | Beta-cell function and regeneration [70] | Melanoma [71] Pancreatic cancer [71] | India (Delhi, Pune) [53] Europeans [53] |
7 | Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) | Regulates cellular metabolism [72] | Obesity [72] Fatty liver [72] Cancer [72] | India (Delhi, Pune); Europeans [53] |
8 | Cdk5 regulatory associated protein 1-like 1 (CDKAL1) | Regulates mitochondrial activity and function in adipose tissue [73] | Pulmonary artery hypertension [74] | India (Delhi, Pune, Hyderabad) [24, 53] Europeans [53] China [59] |
9 | Alkylglycerol Monooxygenase (AGMO) | Catalysing the breakdown of alkylglycerols and lyso-alkyl glycerophospholipids [75] | Adolescent idiopathic scoliosis [75] Cancer [75] Tuberculosis [75] Autism spectrum disorders [75] Microcephaly [75] Neurodevelopmental disorders [75] | African region (South Africa) [16] |
10 | Adiponectin, C1Q And Collagen Domain Containing (ADIPOQ) | increases insulin sensitivity, enhances fatty acid oxidation, glucose uptake in skeletal muscles, reduces glucose uptake in liver [47] | prediabetes [47] Hypertension [76] | Sikh Indians (Punjab, Haryana, Himachal Pradesh, Delhi and Jammu and Kashmir [4]) Eastern Mediterranean (Jordan [47]) |
11 | Insulin-Degrading Enzyme (IDE) | Insulin-degrading enzyme [77] | Alzheimer's diseases [77] | India—Punjab, Jammu and Kashmir, Orissa [54] |
12 | Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) | Negative regulator of insulin activity [28] | Generalized arterial calcification of infancy [78] Hypophosphatemic rickets [78] | India (Punjab, Orissa, Jammu and Kashmir) [54] Europeans [28] |
13 | Alpha-Ketoglutarate-Dependent Dioxygenase (FTO) | encodes for a non-heme and 2-oxoglutarate-dependent oxygenase with nucleic acid demethylase activity [58] | Obesity [26] Obesity related Hypertension [79] Colon cancer [80] | |
14 | Cyclin-Dependent Kinase Inhibitor 2B CDKN2B | Regulation of beta-cell mass, proliferation and insulin secretory function [81] | Glaucoma [82] Coronary artery disease [83] | UK population [27] |
15 | Solute Carrier Family 16 Member 11 (SLC16A11) | Hepatic liver metabolism [84] | Type 2 diabetes [84] | UK population [26] |
16 | Dual specificity phosphatase 9 (DUSP9) | Susceptibility to insulin resistance [85] | Prediabetes [19] Gestational diabetes mellitus [85] | European population [19] |
17 | Kruppel-like factor 14 (KLF14) | Improve insulin sensitivity and increase glucose uptake in Hepa1-6 cells [86] | Prediabetes [19] Metabolic syndrome [86] | European population [19] |
18 | Ribosomal protein S6 kinase alpha-1 (RPS6KA1) | Endothelial dysfunction [48] | Fasting plasma glucose [48] | Eastern Mediterranean (Arab [48]) |
19 | Calcium-dependent secretion activator (CADPS) | Neural/endocrine-specific cytosolic and peripheral membrane protein required for the Ca2+ -regulated exocytosis of secretory vesicles [87] | Bipolar disorder Jejunal Somatostatinoma and Pineoblastoma [87] | Eastern Mediterranean (Arab [48]) |
20 | Valyl-tRNA synthetase (VARS) | Linking amino acids [88] | Fasting plasma glucose [48] Neurodevelopmental disorders with microcephaly [88] Seizures [88] Cortical atrophy [88] | Eastern Mediterranean (Arab [48]) |
21 | DExH-Box Helicase 58 (DHX 58) | Enables double-stranded RNA-binding [48] | – | Eastern Mediterranean (Arab [48]) |
22 | Retinoic acid-inducible gene (STRA6) | Mediate cellular uptake of Vitamin A [89] | Gestational diabetes mellitus [89] | India (Kerala [17]) |
23 | Forkhead box protein A2 (FOXA2) | Insulin resistance [90] | Parkinsonism [90] | India (North Indian [60]) |