Intracellular Adhesion Molecule-1 K469E Gene Polymorphism and Risk of Diabetic Microvascular Complications: A Meta-Analysis

Abstract

BackgroundA number of studies evaluated the association of intracellular adhesion molecule-1 (ICAM-1) K469E (rs5498, A/G) gene polymorphism with diabetic microvascular complications (DMI) including diabetic nephropathy (DN) and diabetic retinopathy (DR) in different populations. However, the results of individual studies remain conflicting.MethodsA comprehensive search was conducted to identify all eligible studies of the above-mentioned associations. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using the fixed or random effect model.ResultsSeven studies involving 3411 subjects were included. Overall, the meta-analysis showed a significant association of the A allele with increased risk of DMI susceptibility in a recessive model (OR = 1.37, 95% CI 1.04–1.80, P = 0.02). In the subgroup analysis stratified by ethnicity, significant association was found in Asians but not in Caucasians (OR = 1.78, 95% CI 1.13–2.81, P = 0.01; OR = 1.10, 95% CI 0.79–1.54, P = 0.58, respectively). Moreover, it showed a significant association between the A allele and risk of DN in a recessive model (OR = 1.25, 95% CI 1.02–1.55, P = 0.04).ConclusionsThis meta-analysis suggested that the K469E polymorphism in ICAM-1 gene might affect individual susceptibility to DMI and showed a discrepancy in different ethnicities. Further investigations are needed to validate the association.

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“…Furthermore, ICAM-1 is expressed on a variety of cells, including endothelial and epithelial cells, fibroblasts, activated T cells, monocytes, macrophages and natural killer cells amongst others, which can enhance the adhesion between monocyte-macrophage and endothelial cells and cause inflammation (23). A continuously increased expression of ICAM-1 can cause serious damage to the structure and function of tissues and organs (24). Furthermore, ICAM-1 molecules are widely present in the body and are expressed in a variety of hematopoietic and non-hematopoietic cells, which are distributed mainly in various epithelial and endothelial cells, fibroblasts, reticular cells, monocytes, macrophages and lymphocytes (25).…”

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“…In addition to its association with sICAM1 levels, the ICAM1 SNP rs5498 has been shown to associate with a plethora of diseases in Asians including diabetic microvascular complications [37], proliferative diabetic retinopathy [38], oral carcinogenesis [39], migraine [40], and coronary atherosclerosis [41]. Because rs5498 encodes a lysine-to-glutamic acid mutation at position 469 (K469E) which alters the electrostatic property of the binding site for ICAM1’s ligand LFA-1 [42], it is likely that changes in ICAM1’s affinity to LFA-1 contribute to the inflammation-related diseases.…”

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“…The inflammatory cascade is triggered by the interactions between various chemokines secreted from resident glomerular cells such as MCP-1 and adhesion molecules such as ICAM-1, leading to the underlying pathological changes in DN (59). This observation has been confirmed using the ICAM-1 and MCP-1 gene knockout diabetic mice, as both exhibited markedly reduced kidney monocytes/macrophages accumulation, which was associated with lowered albuminuria and marked attenuation of renal injury (53).…”