Single nucleotide variations in the development of diabetic foot ulcer: A narrative review

Table 1 Single nucleotide variations involving in the development of diabetic foot and its related complications

Ref.	Population or ethnicity	Total sample size (DF vs T2DM without DF) vs controls	Genes	SNVs reported	Potential influences of the SNVs on DF and DF related complications	Genotypes as risk or protective factors
Wang et al[17], 2020	Chinese	2995 (681 vs 1053 vs 1261)	CRP	rs11265260	Risk factor of DFO	GG + AG/GG
			CRP	rs1800947	Risk factor of DFO	GG + CG
			CRP	rs2794520	Risk factor of DFO	TT + CT/TT
			CRP	rs1130864	Risk factor of DFO	TT + CT/TT
			CRP	rs3093059	Protective factor against DFO	CC+CT/CC
Dhamodharan et al[23], 2015	Indian	515 (2701 vs 139 vs 106)	IL-6	rs1800795	Protective factor against T2DM but not against DFU-DN	GC, CC
Erdogan et al[24], 2017	Turkish	204 (50 vs 35 vs 119)	IL-6	rs1800795	Risk factor of T2DM but not DFU	GG
Viswanathan et al[25], 2018	Indian	270 (without controls)	IL-6	rs1800795	Risk factor of severe wound infections	GC + CC
Dhamodharan et al[23], 2015	Indian	515 (2701 vs 139 vs 106)	TNF-α	rs1800629	Risk factor of both T2DM and DFU-DN	GA, AA
Viswanathan et al[25], 2018	Indian	270 (without controls)	TNF-α	rs1800629	Risk factors of severe wound infections, ulcer grade of DF	GA + AA
				rs361525	Risk factor of ulcer grade of DF	GA + AA
Dhamodharan et al[23], 2015	Indian	515 (2701 vs 139 vs 106)	SDF-1	rs1801157	Protective factor against T2DM and/or DFU-DN	GA, AA: T2DM; AA: DFU-DN
Viswanathan et al[25], 2018	Indian	270 (without controls)	SDF-1	rs1801157	Risk factors of severe wound infections and major amputations (foot/leg)	GA + AA
Amoli et al[34], 2011	Iranian	586 (247 vs 241 vs 98)	VEGF	rs699947	Protective factor against DFU	AA
Li et al[35], 2018	Chinese	288 (97 vs 88 vs 103)	VEGF	rs699947	Protective factor against DFU	AC, AA
Li[36], 2018	Chinese	229 (121 vs 108) (without healthy controls)	VEGF	rs2010963	Protective factor against DFU	CC
Teena et al[42], 2020	Indian	400 (100 vs 150 vs 150)	NRF2	rs35652124	Risk factors of DFU	TT
Teena et al[43], 2021	Indian	400 (100 vs 150 vs 150)	NRF2	rs182428269	Protective factor against T2DM and DFU	CC, CT
					Risk factor of T2DM and DFU	TT
Peng et al[45], 2018	Chinese	438 (142 vs 148 vs 148)	SIRT1	rs12778366	Protective factor against T2DM and DF	Allele C carriers
Cao et al[48], 2020	Chinese	430 (128 vs 147 vs 155)	ICAM1	rs5498	Protective factor against T2DM and DF	GG
			ICAM1	rs3093030	Protective factor against DF	CT + TT
Li[36], 2018	Chinese	229 (121 vs 108) (without healthy controls)	MCP-1	rs1024611	Risk factor of DFU	GG
Su et al[51], 2018	Chinese	400 (116 vs 135 vs 149)	MCP-1	rs1024611	Risk factor of DFU	AG, GG
Sadati et al[53], 2018	Iranian	257 (123 vs 134) (without healthy controls)	eNOS	eNOS Glu298Asp	Protective factor against DFU	TT
Erdogan et al[37], 2018	Turkish	182 (50 vs 57 vs 75)	eNOS	eNOS G894T	Risk factor of T2DM but not DFU	Not related to DFU onset
Zubair and Ahmad[58], 2018	Arabian	150 (50 vs 50 vs 50)	HSP-70	rs2227956	Risk factor of DFU	TT
					Protective factor of DFU	CC
Pichu et al[60], 2015	Indian	224 (79 vs 79 vs 66)	HIF-1α	rs11549465	Risk factor of DFU but not T2DM	CT
Pichu et al[61], 2018	Indian	529 (199 vs 185 vs 145)	HIF-1α	rs11549467	Risk factors of T2DM and DFU	GA
Pichu et al[65], 2017	Indian	906 (301 vs 305 vs 300)	LOX	rs1800449	Risk factor of DFU but not T2DM	AA
Mrozikiewicz-Rakowska et al[66], 2017	Polish	670 (204 vs 299 vs 167)	ITLN1	rs2274907	Risk factor of DF but not T2DM	TT
Meng et al[68], 2017	Scottish	3394 (699 vs 2695)	MAPK14	rs80028505	Risk factor of DFU	Not reported
Wifi et al[71], 2017	Egyptian	90 (30 vs 30 vs 30)	TLRs	rs5743836	Risk factor of DFU among T2DM patients	CT
Singh et al[70], 2013	Indian	255 (125 vs 130) (DFU vs healthy controls)	TLRs	rs4986790	Risk factor of DFU	AG/GG + AG
			TLRs	rs4986791	Risk factor of DFU	TT/CT/CT + TT
			TLRs	rs11536858	Risk factor of DFU	GG/AG/GG + AG
			TLRs	rs1927914	Risk factor of DFU	CC
			TLRs	rs1927911	Risk factor of DFU	CT/CT + TT
Nehring et al[72], 2013	Polish	877 (122 vs 293 vs 462)	OPG	rs2073617	Protective factor against DF among female patients	AG
			OPG	rs2073618	Risk factor of DF among T2DM patients	CC
Soroush et al[76], 2017	Iranian	212 (105 vs 107) (without healthy controls)	VDR	rs2228570	Risk factor of DFU among T2DM patients	TT + CT
Zhao et al[78], 2015	Chinese	300 (123 vs 97 vs 80)	FIB	rs6056	Risk factor of DF	CT, TT

¹This group of 270 patients included 191 patients with DFU-DN and 79 patients with DFU-peripheral vascular disease.

DF: Diabetic foot; T2DM: Type 2 diabetes mellitus; SNVs: Single Nucleotide Variations; DFO: Diabetic foot osteomyelitis; DFU-DN: Diabetic foot ulcer with diabetic neuropathy; CRP: C-reactive protein; IL-6: Interleukin-6; TNF-α: Tumor Necrosis Factor-Alpha; SDF-1: Stromal cell Derived Factor-1; VEGF: Vascular Endothelial Growth Factor; NRF2: Nuclear Factor Erythroid-2-related Factor 2; SIRT1: Sirtuin 1; ICAM1: Intercellular Adhesion Molecule 1; MCP-1: Monocyte Chemoattractant Protein-1; eNOS: Endothelial Nitric Oxide Synthase; HSP-70: Heat Shock Protein-70; HIF-1α: Hypoxia inducible factor 1 alpha; LOX: Lysyl Oxidase; ITLN1: Intelectin 1 (Omentin); MAPK14: Mitogen-activated Protein Kinase 14; TLRs: Toll-Like receptors; OPG: Osteoprotegerin; VDR: Vitamin D receptor; FIB: Fibrinogen.