Diabetes: A comprehensive review of the Indian landscape in contrast with global trends

Table 3 Genes associated with type 1 diabetes, type 2 diabetes, and gestational diabetes

Genes associated with type 1 diabetes
Ref.	Ke et al[39], 2022; Nejentsev et al[40], 2009
Gene Symbol	Key function/mechanism	Variant types	Clinical significance	Primary population-specific data
HLA	Antigen presentation; strongest genetic risk factor	HLA Haplotypes	High-risk alleles	European, Scandinavian, Hispanic
INS	Thymic insulin expression; immune tolerance	VNTR	Risk alleles	European, Asian
IL2RA	Altered Treg function and immune tolerance	SNPs	Risk alleles	European, Asian
PTPN22	Reduced inhibitory signaling in lymphocytes	SNPs	Risk alleles	European, Asian
IFIH1	Viral RNA sensor; reduced antiviral response	Rare Variants	Protective alleles	European
BACH2	Affects lymphocyte development; autoimmunity	SNPs	Risk alleles	European
TYK2	Influences beta-cell survival and immune responses	SNPs	Risk alleles	European
CLEC16A	Impaired autophagy affects antigen presentation	SNPs	Risk alleles	European
CD226	T-cell activation	SNPs	Risk alleles	European
CCR5	Chemokine receptor; T-cell migration	Deletion (Δ32)	Protective allele	European
CTLA4	Immune checkpoint regulation	SNPs	Risk alleles	Various populations
STAT4	Signal transduction in inflammatory responses	SNPs	Risk alleles	Various populations
EPO	Linked to T1D complications (nephropathy)	SNPs	Risk alleles	Various populations
NOS3	Associated with vascular complications	SNPs	Risk alleles	Various populations
MIR375	MicroRNA regulating insulin secretion & beta-cell mass	MicroRNA	Regulatory role	Various populations
Genes associated with type 2 diabetes
Ref.	Gloyn et al[41], 2003; Dornbos et al[42], 2022; Kumar et al[43], 2024; Flannick et al[44], 2019; Shi et al[45], 2025; Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research et al[46], 2007; Abu Aqel et al[47], 2024; Russ-Silsby et al[48], 2025; Gerber et al[49], 2017; Fuchsberger et al[50], 2016; Hwang et al[51], 2023; Udler et al[52], 2019; Morris et al[53], 2012
TCF7 L2	Wnt signaling regulates insulin secretion	SNPs	Strongest common risk allele	European, Hispanic, Asian
PPARG	Nuclear receptor; influences insulin sensitivity	Missense (Pro12Ala)	Risk and Protective alleles	Predominantly European
SLC30A8	Zinc transporter in insulin granules	Loss-of-function	Protective allele	Multiethnic cohorts
KCNJ11	Potassium channel regulates insulin secretion	Missense (E23K)	Confirmed risk allele	Global distribution
FTO	Regulates appetite and adiposity	Intronic SNPs	Risk allele via obesity	Worldwide (strongest in Europeans)
GCK	Glucose-sensing enzyme; modulates β-cell function	Missense, Nonsense	Risk and rare MODY alleles	European populations
MTNR1B	Melatonin receptor; impairs insulin secretion	SNPs	Risk alleles	European and Asian populations
IRS1	Mediates insulin signaling; insulin resistance	SNPs	Risk allele	European and Asian populations
HHEX	Pancreas development; impaired insulin secretion	SNPs	Risk alleles	Asian and European populations
CDKAL1	β-cell insulin secretion regulator	SNPs	Risk alleles	European populations
KCNQ1	Potassium channel; affects β-cell electrical activity	SNPs	Risk alleles	East Asian populations
WFS1	Linked to beta-cell survival and apoptosis	SNPs	Risk alleles	European populations
ANK1	Linked to insulin secretion defects	SNPs	Risk alleles	European populations
GIPR	Influences insulin release and glucose tolerance	Missense, SNPs	Risk alleles	European populations
PDX1	Influences beta-cell function and development	SNPs	Risk alleles	European populations
Genes associated with gestational diabetes
Ref.	Lu et al[54], 2024; Keels et al[55], 2024; Liang et al[56], 2024; Mittal et al[57], 2025; Fan et al[58], 2021; Sladek et al[59], 2007; Gwenzi and Brenner[60], 2024; Li et al[61], 2020; Goyal et al[62], 2023; Saini[63], 2010; Sayyed Kassem et al[64], 2023
TCF7 L2	Wnt signaling regulates insulin secretion	SNPs	Higher susceptibility to GDM	Chinese Han population
MTNR1B	Melatonin receptor; influences circadian rhythm	SNPs	Elevated fasting glucose; GDM risk	Russian women
GCK	Glucose-sensing enzyme in β-cells	SNPs	Impaired glucose sensing and GDM	Multiple populations
IRS1	Mediates insulin signaling; insulin resistance	SNPs	Increased insulin resistance; GDM	Multiple populations
KCNJ11	Potassium channel; insulin release	SNPs	Altered secretion; GDM risk	Multiple populations
CDKAL1	β-cell insulin secretion regulator	SNPs	Impaired secretion; GDM risk	Women < 30 years
HHEX	Pancreas development regulator	SNPs	Increased GDM risk	Multiple populations
SLC30A8	Zinc transporter in insulin granules	SNPs	Defective insulin storage; GDM	North Indian population
CDKN2A/2B	Regulate β-cell cycle; impair proliferation	SNPs	Increased GDM risk	Multiple populations
KCNQ1	Potassium channel; β-cell function	SNPs	Altered insulin secretion	Multiple populations
HNF1B	Transcription factor for pancreas development	SNPs	Reduced insulin secretion	Multiple populations
ABCC8	Regulates insulin secretion via K⁺ channels	SNPs	Disrupted insulin control; GDM	Multiple populations
KIAA0825	Potential oncogene; linked to high glucose	SNPs	Elevated glucose levels	Chinese Han population
FOXC2	Adipocyte differentiation and insulin sensitivity	SNPs	Protective effect against GDM	Multiple populations
HKDC1	Hexokinase is involved in glucose metabolism	SNPs	Impaired glucose metabolism; GDM risk	Multiple populations
TRA2A, NPM3, PHF5A, PLXNA3	RNA splicing, cell cycle, signaling (biomarkers)	SNPs	Diagnostic utility for GDM	Multiple populations

HLA: Human leukocyte antigen; T1D: Type 1 diabetes; INS: Insulin; VNTR: Variable Number Tandem Repeat; IL: Interleukin; SNPs: Single nucleotide polymorphism; PTPN22: Protein tyrosine phosphatase non-receptor type 22; IFIH1: Interferon induced with helicase C domain 1; BACN2: BTB domain and CNC homolog 2; TYK2: Tyrosine kinase 2; CLEC6A: C-type lectin domain containing 16A; CCR5: C-C motif chemokine receptor 5; HIV: Human immunodeficiency virus; CTLA4: Cytotoxic T-lymphocyte associated protein 4; STAT4: Signal transducer and activator of transcription 4; EPO: Erythropoietin; NOS3: Nitric oxide synthase 3; TCF7 L2: Transcription factor 7 like 2; PPARG: Peroxisome proliferator-activated receptor gamma; SLC30A8: Solute carrier family 30 member 8; KCNJ11: Potassium inwardly rectifying channel subfamily J member 11; FTO: Fat mass and obesity associated gene; GCK: Glucokinase; MTNR1B: Melatonin receptor 1B; IRS1: Insulin receptor substrate 1; HHEX: Hematopoietically expressed homeobox; PDX1: Pancreatic and duodenal homeobox 1; KCNQ1: Potassium voltage-gated channel subfamily Q member 1; CDKAL1: Cyclin dependent kinase 5 regulatory subunit associated protein 1-like 1; WFS1: Wolframin ER transmembrane glycoprotein; ANK1: Ankyrin 1; GIPR: Gastric inhibitory polypeptide receptor; T2D: Type 2 diabetes; MODY: Maturity Onset Diabetes of the Young; CDKN2A/CDKN2B: Cyclin dependent kinase inhibitor 2A/2B; HNF1B: Hepatocyte nuclear factor 1 beta; ABCC8: ATP-binding cassette subfamily C member 8; FOXC2: Forkhead Box C2; TRA2A: Transformer 2 alpha homolog; NPM3: Nucleophosmin/nucleoplasmin 3; PHF5A: PHD-finger domain protein 5 A; PLXNA3: Plexin A3; HKDC1: Hexokinase domain containing 1; GDM: Gestational diabetes.