Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

Table 1 Variants of interleukin-1 gene cluster (interleukin-1α, interleukin-1β, interleukin-1Ra, interleukin-18) and their association with type 2 diabetes in different populations

Gene	Variants (SNPs)	Population-Ethnic group	Association	Ref.
IL-1α	-889		NS	[26]
IL-1β	3954
IL-1β	-511
IL-1Ra	VNTR
IL-1α	3'UTR	Caucasians and African Americans	S	[27]
IL-1	C-889T	East Indian	S	[28]
IL-1β	C-511T
IL-1β	C3953T
IL-1α			S	[29]
IL-Ra	VNTR
IL-1β	C3954T		S	[30]
IL-1β	-511	North Indian	S	[31]
IL-1Ra	VNTR
IL-1β	C-511T		S	[32]
IL-1Ra	VNTR
IL-1β	C-511T	Korean	S	[33]
IL-1Ra	VNTR
IL-1Ra	VNTR		NS	[29]
IL-1Ra	VNTR		S	[34]
IL-1Ra	VNTR	North Indian	S	[17]
IL-1Ra	VNTR	Caucasians	NS	[35]
IL-1Ra	VNTR		S	[36]
IL-1RI	PstI, HinfI, AluI (promoter region)	Dalmatian population of South Croatia	S	[37]
	PstI (exon 1B region)
IL-18	+183 A/G	Norwegian	S	[38]
	-137 G/C		NS
	-607 C/A		NS
	-607 C/A	Chinese	S	[39]
	BCO2	European	S	[40]
	rs2250417	European	NS	[41]
	5 SNPs	European	S	[42]

UTR: Untranslated region; VNTR: Variable number of tandem repeats; S: Significant; NS: Nonsignificant; IL-1: Interleukin-1; SNPs: Single nucleotide polymorphisms.

Table 2 Variants of interleukin-4 gene and their association with type 2 diabetes in different populations

Gene variants (SNPs)	Disease	Population-Ethnic groups	Association	Ref.
-590 C/T	T2DM	Iranian	S	[64]
-589 C/T	T2DM	Chinese	S	[65]
-34 C/T	T2DM
VNTR	T2DM	North Indian	S	[17]

VNTR: Variable number of tandem repeats; S: Significant; T2DM: Type 2 diabetes; SNPs: Single nucleotide polymorphisms.

Table 3 Variants of Interleukin-6 gene and their association with type 2 diabetes and related complications in different populations

Gene variants (SNPs)	Diseases	Population- Ethnic groups	Association	Ref.
-174 G/C	T2DM and OGTT	Brazilian	S	[77]
	T2DM and IR	American	S	[78]
	T2DM and obesity	Polish	S	[79]
	T2DM and obesity	Mexican	NS	[80]
	T2DM	Indian	S	[81]
	T2DM	Finnish	NS	[82]
	T2DM and Obesity	Tunisian	S	[83]
	T2DM	Caucasian	S	[84]
	T2DM	German	S	[85]
	DM, micro-, macrovascular complications	Australian	NS	[29]
	-do-	German	NS	[86]
	T2DM and IR	Italian	S	[87]
	T2DM	KORA Survey	S	[88]
	T2DM	Framingham Heart Study	S	[89]
	T2DM	KORA Survey	S	[90]
	T2DM	Taiwanese	S	[91]
	T2DM	Nutrition-Potsdam cohort	S	[92]
	T2DM	Finnish	S	[93]
	T2DM	Native Americans, Spanish, Caucasians	S	[75]
	T2DM and IR	Spanish	S	[94]
	T2DM and PAD	Italian	S	[95]
	T2DM	KORA Survey	S	[76]
	DM and Periodontitis	Chinese	S	[96]
	T2DM and Endothelial Dysfunction	Chinese	S	[97]
	T2DM	21 studies	S	[71]
-174 G/C -597 A/G	T2DM	Boston	NS	[98]
GWS (18 SNPs)	T2DM	Canadian	S with Fasting	[99]
PREDIAN study	DN	Spanish	S	[100]
Five tagging SNPs	T2DM and Impaired Renal Function	Singaporean	S	[101]

S: Significant; NS: Non-significant; T2DM: Type 2 diabetes; PAD: Peripheral arterial disease; SNPs: Single nucleotide polymorphisms; OGTT: Oral glucose tolerance test; DM: Diabetes mellitus; IR: Insulin resistance; DN: Diabetic nephropathy.

Table 4 Variants of interleukin-10 gene and their association with type 2 diabetes and related complications in different populations

Gene variants (SNPs)	Diseases	Population- Ethnic groups	Association	Ref.
-592 A/C	T2DM	Iranian	NS	[108]
	T2DM	Chinese	NS	[109]
	T2DM	North Indian	S	[4]
-1082 G/A	proliferative diabetic retinopathy	Indian	S	[110]
	T2DM	South Indian	S	[111]
-1082 G/A -819 C/T -592 C/A	T2DM	Caucasian Italian	S	[112]
-1082 G/A	T2DM	Turkish	NS	[113]
-1082 G/A -819 C/T -592 C/A	T2DM	Greek	NS	[106]
-592 A/C -819 C/T	T2DM	Taiwanese	NS	[107]
-592 A/C	T2DM	Taiwanese	S	[114]
-1087 G/A -824 C/T -597 C/A	T2DM	Italian	S	[115]
-592 A/C	T2DM	Tunisian	S	[18]

S: Significant; NS: Non-significant; T2DM: Type 2 diabetes; SNPs: Single nucleotide polymorphisms.

Table 5 Variants of tumor necrosis factor-α gene and their association with type 2 diabetes and related complications in different populations

Gene variation (SNPs)	Diseases	Population- Ethnic groups	Association	Ref.
G-308A	T2DM	Tarragona	S	[120]
	T2DM	Taiwanese	S	[121]
	T2DM	Croatian Caucasians	S	[122]
	T2DM and peridontitis	Chinese	S	[123]
	T2DM, MS and Obesity	Indian	S	[124]
	T2DM	Mexican	S	[125]
	Glucose metabolism	Brazilian	S	[126]
	T2DM	Japanese	NS	[127]
	T2DM	Mexican	NS	[128]
	T2DM	Chinese	NS	[129]
	T2DM	Greek	NS	[130]
	atherosclerotic diabetic	Hungarian	S	[131]
	T2DM	Indian	S	[81]
	T2DM	United Kingdom/Irish	NS	[132]
	T2DM	Finnish	S	[82]
sTNFR1 and sTNFR2	Glucose metabolism	Hungarian	NS	[133]
C-857T	IR and T2DM	Japanese	S	[134]

S: Significant; NS: Non-significant; T2DM: Type 2 diabetes; SNPs: Single nucleotide polymorphisms; MS: Metabolic syndrome; TNFR1: Tumor necrosis factor receptor 1.

Table 6 Variants of adiponectin gene and their association with type 2 diabetes and related complications in different populations

Gene variants (SNPs)	Diseases	Population- Ethnic groups	Association	Ref.
+45 G/T	Obesity	Iranians	NS	[146]
	T2DM	Malaysian	S	[147]
	T2DM	Greek	NS	[148]
	MS	Chinese	S	[149]
	T2DM	Japanese	NS	[150]
	T2DM	Chinese	S	[151]
	Non-T2DM	Caucasian Canadians	NS	[152]
	T2DM	Hispanic Americans	NS	[153]
	T2DM	French Caucasian	NS	[154]
	T2DM	Korean	NS	[155]
	T2DM	Caucasians	S	[154]
	T2DM	Spanish	NS	[156]
	IGT	European/Canadian	NS	[157]
	Non-T2DM	Japanese	NS	[158]
	Obesity	Swedish	NS	[159]
	T2DM	Caucasian Italians	NS	[160]
	T2DM	Caucasian Italians	NS	[161]
	T2DM	Pima Indians	NS	[162]
	T2DM	European Caucasians	NS	[163]
	T2DM	French Caucasians	S	[164]
+10211 T/G	T2DM	Asian Indians	S	[165]

S: Significant; NS: Non-significant; T2DM: Type 2 diabetes; SNPs: Single nucleotide polymorphisms; MS: Metabolic syndrome; IGT: Impaired glucose tolerance.