Recent advances in the molecular genetics of type 2 diabetes mellitus

Table 1 Type 2 diabetes mellitus susceptibility genes

Gene	Chr	Odds ratio	RAF	Study	Function and probable mechanism	Ref
ADAMTS9	3	1.09-1.05	0.68-0.81	MA	Metalloproteinase/Insulin action	[22–24]
ADCY5	3	1.12	0.78	MA	Adenylyl cyclases/Insulin action	[25]
ANK1	8	1.09	0.76	MA, CC	Cell stability/β-cell function	[26–28]
ANKRD55	5	1.08	0.7	MA, CC	Insulin action	[26,27]
ANKS1A	6	1.11	0.91	GWAS	Pathway regulator/Unknown	[29]
ARAP1	11	1.08-1.14	0.81-0.88	GWAS, MA	Actin cytoskeleton modulator/β-cell function	[22,24]
BCAR1	16	1.12	0.89	MA, CC	Docking protein/β-cell function	[26,27]
BCL2	18	1.09	0.64	GWAS	Cell death regulator/Unknown	[24]
BCL11A	2	1.08-1.09	0.46	MA	Zinc finger/β-cell function	[22]
CAMK1DCDC123	10	1.07-1.11	0.18	LA, MA	Protein kinase/β-cell function	[22–24]
					Mitotic protein/β-cell function
CAPN10	2	1.09-1.18	0.73-0.96	MA	Calpain cysteine protease/Insulin action	[30–33]
CDKAL1	6	1.10-1.20	0.27-0.31	GWAS, MA	β-cell function	[24,34–36]
CDKN2ACDKN2B	9	1.19-1.20	0.82-0.83	GWAS	Cyclin-dependent kinase inhibitor/β-cell function	[24,34,35]
CENTD2	11	1.08-1.13	0.81-0.88	GWAS	β-cell function	[22,24]
CHCHD9TLE4	9	1.11-1.20	0.93	MA	Unknown	[22]
CILP2	19	1.13	0.08	MA, CC	Unknown	[26,27]
DGKB	7	1.04-1.06	0.47-0.54	MA	Diacylglycerol kinase/Insulin action	[24,25]
DUSP9	X	1.09-1.27	0.12-0.77	MA	Phosphatase	[22,24]
FOLH1	11	1.10	0.09	GWAS	Transmembrane glycoprotein/Unknown	[24]
FTO	16	1.06-1.27	0.38-0.41	GWAS, MA	Metabolic regulator/Insulin action	[24,37]
GATAD2A	19	1.12	0.08	GWAS	Transcriptional repressor/Unknown	[24]
GCK	7	1.07	0.20	MA	Glucokinase/Insulin action	[25]
GCKR	2	1.06-1.09	0.59-0.62	MA	Glucokinase regulator/Insulin action	[24,25]
GIPR	19	1.10	0.27	GWAS	G-protein coupled receptor/Unknown	[24]
GRB14	2	1.07	0.60	MA, GCS	Adapter protein/Insulin action	[26,27]
HFE	6	1.12	0.29	MA	Membrane protein/Unknown	[38]
HHEX	10	1.12-1.13	0.53-0.60	AL, MA	Transcriptional repressor/	[22,24,34,39]
IDE					Intracellular insulin degradation/
KIF11					Motor protein
HMG20A	15	1.08	0.68	MA, GCS	Chromatin-associated protein/Unknown	[26,27]
HMGA1	6	1.34-15.8	0.10	GCS	Transcriptional regulator/Insulin action	[40-42]
HMGA2	12	1.10-1.20	0.09-0.10	MA	Transcriptional regulator	[22,24]
HNF1A	12	1.07-1.14	0.77-0.85	MA	Pancreatic and liver transcriptional activator	[22,24]
HNF1B	17	1.08-1.17	0.47-0.51	GCS, MA	Transcription factor/β-cell function	[22,24]
IGF2BP2	3	1.14	0.29-0.32	GWAS, MA	Binding protein/β-cell function	[22,24,34,35]
IRS1	2	1.09-1.12	0.64-0.67	GCS, MA	Insulin signaling element/Insulin action	[22,24,43]
JAZF1	7	1.10	0.52	MA	Zinc finger/β-cell function	[22,23]
KCNJ11	11	1.09-1.14	0.37-0.47	GCS, MA	Potassium channel/β-cell function	[22,24,34,44]
KCNQ1	11	1.08-1.23	0.44	GWAS	Potassium channel/β-cell function	[22,45,46]
KLF14	7	1.07-1.10	0.55	MA	Transcription factor/Insulin action	[22]
KLHDC5	12	1.10	0.80	MA, CC	Mitotic progression and cytokinesis/Unknown	[26,27]
LAMA1	18	1.13	0.38	GWAS	Cellular migration mediator/Unknown	[29]
MC4R	18	1.08	0.27	MA, CC	G-protein–coupled receptor/Unknown	[26,27]
MTNR1B	11	1.05-1.08	0.28-0.30	GWAS, MA	Melatonin receptor/β-cell function	[24,47-49]
NOTCH2	1	1.06-1.13	0.10-0.11	MA	Membrane receptor	[22-24]
PPARG	3	1.11-1.17	0.85-0.88	GCS, MA	Nuclear receptor/Insulin action	[22,24,34,50]
PRC1	15	1.07-1.10	0.22	MA	Cytokinesis regulator	[22]
PROX1	1	1.07	0.50	MA	Homeobox transcription factor/Insulin action	[25]
PTPRD	9	1.57	0.10	GWAS	Protein tyrosine phosphatase	[51]
RBMS1	2	1.11-1.08	0.79-0.83	MA	DNA modulator/Insulin action	[24,52]
SLC2A2	3	1.06	0.74	GWAS	Glucose sensor/β-cell function	[24]
SLC30A8	8	1.11-1.18	0.65-0.70	GWAS, MA	Zinc efflux transporter/β-cell function	[22,24,25,34,53]
SREBF1	17	1.07	0.38	GWAS	Lipid transcriptional regulator/Unknown	[24]
SRR	17	1.28	0.69	GWAS	Serine racemase	[51]
TCF7L2	10	1.31-1.71	0.26-0.30	LA, MA,GWAS	Participates in the Wnt signaling pathway/β-cell function	[21,22,24,34]
THADA	2	1.15	0.90	MA	Thyroid adenoma-associated protein/β-cell function	[22-24]
TH/INS	11	1.14	0.39	GWAS	Catecholamine synthesis/Unknown	[24]
TLE1	9	1.07	0.57	MA, CC	Transcriptional corepressor/Unknown	[26,27]
TP53INP1	8	1.06-1.11	0.48	MA	Proapoptotic protein/Unknown	[22]
TSPAN8	12	1.06-1.09	0.27-0.71	MA	Cell surface glycoprotein/β-cell function	[22-24]
LGR5					G-protein coupled receptor/β-cell function
WFS1	4	1.10-1.13	0.60-0.73	GCS	Transmembrane protein/β-cell function	[22,24,54,55]
ZBED3	5	1.08-1.16	0.26	MA	Zinc finger/b-cell function	[22]
ZFAND6	15	1.01-1.11	0.60-0.72	MA	Zinc finger/β-cell function	[22,24]
ZMIZ1	10	1.08	0.52	MA, CC	Transcriptional regulator/Unknown	[26,27]
Haplogroup B	mtDNA	1.52	0.25	GCS		[56]
OriB	mtDNA	1.10	0.30	MA		[57]

Chr: Chromosome; MA: Meta-analysis; LA: Linkage analysis; GWAS: Genome-wide association study; GCS: Gene candidate study.