Association of ICAM-1 Gene Polymorphisms with Diabetic Retinopathy in T2DM Patients from Northern India: Case-control and meta-analysis

Table 1 Allele frequencies and genotype distribution of c.1405A>G (p.Lys469Glu) (rs5498) polymorphism in intercellular adhesion molecule-1 in diabetic retinopathy cases and controls

	DR cases, n = 302	CDR, n = 312	χ2, P value	OR (95%CI)	OR, P value
Alleles
A	344 (56.95)	388 (62.17)	0.070	Reference
G	260 (43.04)	236 (37.82)		1.24 (0.98-1.56)	0.062
Genotypes
AA	103 (34.10)	120 (38.46)	0.120	Reference
AG	138 (45.69)	148 (47.43)		1.08 (0.76-1.54)	0.643
GG	61 (20.19)	44 (14.10)		1.61 (1.01-2.58)	0.044a
Genetic models
Dominant model (AA vs AG + GG)				0.98 (0.67-1.42)	0.916
Codominant model (AG vs AA + GG)				0.83 (0.58-1.20)	0.342
Recessive model (GG vs AG + AA)				1.31 (0.81-2.13)	0.262

^aP < 0.05.

Data are presented as n (%). Data indicate the number of subjects with each genotype and allele (frequency in percent). Odds ratios for different modes of inheritance were calculated. Odds ratios were adjusted for age, age of onset of diabetes, duration of diabetes, systolic blood pressure, diastolic blood pressure, random blood glucose levels, glycated hemoglobin, and body mass index. DR: Diabetic retinopathy; CDR: Controls without diabetic retinopathy; OR: Odds ratio; CI: Confidence interval.

Table 2 Allele frequencies and genotype distribution of c.1405A>G (p.Lys469Glu) (rs5498) polymorphism in intercellular adhesion molecule-1 in proliferative diabetic retinopathy and non-proliferative diabetic retinopathy groups

	PDR cases, n = 189	NPDR, n = 113	χ2, P value	OR (95%CI)	OR, P value
Alleles
A	219 (57.93)	125 (55.30)	0.585	Reference	Reference
G	159 (42.06)	101 (44.69)		0.89 (0.64-1.25)	0.528
Genotypes
AA	65 (34.39)	38 (33.62)	0.627	Reference	Reference
AG	89 (47.08)	49 (43.36)		1.06 (0.62-1.80)	0.824
GG	35 (18.51)	26 (23.00)		0.78 (0.41-1.50)	0.467
Genetic models
Dominant model (AA vs AG + GG)				0.93 (0.56-1.54)	0.791
Codominant model (AG vs AA + GG)				1.15 (0.72-1.86)	0.544
Recessive model (GG vs AG + AA)				0.72 (0.40-1.30)	0.285

Data are presented as n (%). Data indicate the number of subjects with each genotype and allele (frequency in percent). Odds ratios for different modes of inheritance were calculated. Odds ratios were adjusted for age, age of onset of diabetes, duration of diabetes, systolic blood pressure, diastolic blood pressure, random blood glucose levels, glycated hemoglobin, and body mass index. PDR: Proliferative diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy; OR: Odds ratio; CI: Confidence interval.

Table 3 Allele frequencies and genotype distribution of c.721G>A (p.Gly241Arg) (rs1799969) polymorphism in intercellular adhesion molecule-1 in diabetic retinopathy cases and controls

	DR cases, n = 302	CDR, n = 312	χ2, P value	OR (95%CI)	OR, P value
Alleles
G	582 (96.35)	622 (99.67)	0.003a	Reference	Reference
A	19 (3.14)	2 (0.32)		-	-
Genotypes
GG	283 (93.7)	310 (99.35)	-	Reference	Reference
GA	19 (6.29)	2 (0.64)		-	-
AA	-	-		-	-
Genetic models
Dominant model (GG vs GA/AA)				-	-
Codominant model (GG vs GA = AA vs GA)				-	-
Recessive model (AA vs GA/GG)				-	-

^aP < 0.05.

Data are presented as n (%). Data indicate the number of subjects with each genotype and allele (frequency in percent). Odds ratios for different modes of inheritance were calculated. Odds ratios were adjusted for age, age of onset of diabetes, duration of diabetes, systolic blood pressure, diastolic blood pressure, random blood glucose levels, glycated hemoglobin, and body mass index. DR: Diabetic retinopathy; CDR: Controls without diabetic retinopathy; OR: Odds ratio; CI: Confidence interval.

Table 4 Comparison of mean values for clinical characteristics stratified by genotypes among diabetic retinopathy cases for intercellular adhesion molecule-1 c.1405A>G (p.Lys469Glu) polymorphism

Characteristics	AA (n = 103)	AG (n = 138)	GG (n = 61)	P value
Age (years)	56.10 ± 8.22	54.93 ± 8.42	55.55 ± 7.92	0.55
Age of onset of diabetes (years)	44.17 ± 10.09	41.63 ± 9.45	42.16 ± 8.91	0.118
Duration of diabetes (years)	11.76 ± 6.27	13.02 ± 5.99	13.63 ± 5.92	0.12
Systolic blood pressure (mmHg)	132.61 ± 13.15	130.28 ± 14.82	134.69 ± 16.58	0.129
Diastolic blood pressure (mmHg)	81.42 ± 6.12	82.12 ± 6.48	82.93 ± 6.17	0.33
BMI (kg/m2)	24.58 ± 3.71	24.05 ± 3.95	23.97 ± 3.13	0.465
Random blood glucose levels (mg/dL)	198.65 ± 68.14	201.62 ± 77.81	187.92 ± 70.01	0.472
HbA1c (%)	8.13 ± 1.12	8.15 ± 1.24	7.94 ± 1.00	0.483
Cholesterol (mg/dL)	130.42 ± 56.24	126.67 ± 52.13	134.46 ± 56.07	0.634
TG (mg/dL)	154.92 ± 70.02	161.48 ± 82.99	156.78 ± 77.16	0.799
High density lipoprotein cholesterol (mg/dL)	41.67 ± 19.07	39.08 ± 21.32	45.90 ± 18.66	0.087
Low density lipoprotein cholesterol (mg/dL)	93.43 ± 61.61	91.93 ± 63.60	96.43 ± 70.28	0.902
Very low density lipoprotein cholesterol (mg/dL)	32.58 ± 15.19	33.18 ± 16.89	32.99 ± 16.74	0.961

Data are presented as mean ± SD. P values were computed by the one-way analysis of variance and indicate the significance of comparison between patients with diabetic retinopathy. BMI: Body mass index; HbA1c: Glycated hemoglobin; TG: Triglyceride.

Table 5 Characteristics of the studies assessing the association between intercellular adhesion molecule-1 Lys469Glu variant and the risk of diabetic retinopathy

No.	Ethnicity	Country	Genotyping	Diabetic retinopathy			Non-diabetic retinopathy			HWE P values	Ref.
				AA	AG	GG	AA	AG	GG
1	Asian	Japan	PCR-RFLP	34	35	12	10	30	10	0.157	Kamiuchi et al[30], 2002
2	Asian	China	PCR-HA SSCP	81	40	11	16	15	9	0.152	Liu et al[27], 2006
3	Caucasian	Slovenia	PCR-RFLP	47	96	52	44	77	22	0.218	Petrovic et al[31], 2008
4	Asian	India	Snapshot	103	162	80	99	174	86	0.578	Balasubbu et al[32], 2010
5	Asian	China	Allele specific PCR	10	24	6	24	14	2	0.982	Zhu et al[28], 2010
6	Asian	China	PCR-RFLP	37	44	21	54	45	21	0.039	Zhou et al[29], 2010
7	Asian	India	DNA sequencing	60	92	47	29	84	44	0.317	Vinita et al[26], 2012
8	Asian	China	PCR-LDR	221	193	34	166	154	24	0.142	Lv et al[25], 2016
9	Asian	India	PCR-RFLP	103	138	61	120	148	44	0.879	Present study

HWE: Hardy-Weinberg equilibrium; PCR-RFLP: PCR-restriction fragment length polymorphism; PCR-HA SSCP: PCR-heteroduplex-single-strand conformation polymorphism; PCR-LDR: PCR-ligase detection reaction.

Table 6 Meta-analysis results of intercellular adhesion molecule-1 Lys469Glu polymorphism under different genetic models in overall and Asian populations

Model		Allelic model (G vs A)			Recessive model (GG vs AG + AA)			Dominant model (AG + GG vs AA)
Ethnicity		Overall	Asian	Caucasian	Overall	Asian	Caucasian	Overall	Asian	Caucasian
Number of studies		9	8	1	9	8	1	9	8	1
Test of association	Model	Random	Random	Fixed	Random	Random	Fixed	Random	Random	Fixed
	OR (95%CI)	0.99 (0.79-1.26)	0.94 (0.74-1.21)	1.44 (1.06-1.95)	1.08 (0.80-1.47)	0.99 (0.74-1.34)	2 (1.15-3.48)	0.951 (0.69-1.31)	0.90 (0.64-1.28)	1.40 (0.86-2.27)
	P value	0.987	0.679	0.021	0.623	0.961	0.014	0.951	0.566	0.173
Test of heterogeneity	I2	0.79	0.79	NA	0.57	0.48	NA	0.76	0.77	NA
	P value	< 0.001	< 0.001	NA	0.02	0.06	NA	< 0.001	< 0.001	NA
Egger’s test P value		0.866	0.796	NA	0.852	0.759	NA	0.857	0.782	NA

OR: Odds ratio; CI: Confidence interval.