Polymorphism rs5498 of the ICAM-1 gene affects the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus

Abstract

BackgroundAdhesion molecules are involved in the development of atherosclerosis. An increased level of the ICAM 1 molecule is associated with numerous inflammatory diseases including atherosclerosis of carotid arteries. The rs5498 (K469E) polymorphism of the ICAM-1 gene leads to an increase in the level of serum ICAM. We investigated the association between the rs5498 (K469E) polymorphism of the ICAM-1 gene and the progression of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). MethodsThe study included 595 patients with T2DM and 200 subjects in the control group without T2DM. The control examination was made 3.8 years after the initial examination. Indicators of atherosclerosis (carotid intima-media thickness (CIMT), total plaque sum and sum of the plaques thickness) were detected by ultrasound examination. Genetic analyses of the polymorphism rs5498 of the ICAM-1 gene were made by RT-PCR.ResultsThe distribution of genotypes and frequencies of rs5498 polymorphism was not significantly different between the group with type 2 diabetes ( T2DM) and the control group. Genotype EE K469E polymorphism is associated with a statistically significant annual plaques growth.ConclusionThe EE genotype of the rs5498 of the ICAM-1 gene was associated with a more rapid progression of carotid atherosclerosis in patients with T2DM in comparison with other genotypes.

Association between K469E polymorphism of ICAM‐1 gene and susceptibility of ischemic stroke: An updated meta‐analysis

“…Similarly, Gaetani et al showed that the presence of the EE genotype significantly independently increased the risk of PAOD (Gaetani et al, 2002). Popović et al in their study found that the EE genotype of the K469E polymorphism of the ICAM-1 gene was associated with a more rapid progression of carotid atherosclerosis in patients with type 2 diabetes mellitus than other genotypes (Gaspar et al, 2016).…”

Association between intercellular adhesion molecule 1 (ICAM1) polymorphisms and diabetic foot susceptibility

“…[ 24 ] Popović and colleagues suggested that rs5498 SNP was not significantly correlated with T2DM susceptibility, but its AA genotype was positively associated with annual plaques growth in T2DM patients. [ 25 ] However, a meta-analysis performed by Fan and Liu indicated that rs5498 G allele carriers had lower susceptibility to DR in Asians than those with A allele. [ 26 ] This SNP was also detected in other diseases.…”

Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

“…candidate genes of inflammation, oxidative stress, growth factors, renin-angiotensin aldosterone system, and so-forth) has so far been demonstrated in several reports to affect the development of atherosclerosis [2]. Genetic variability in the candidate genes implicated in atherosclerosis may alter their transcriptional activity and contribute to susceptibility to cardiovascular disease [3][4][5][6][7][8][9][10][11]. In the pathogenesis of atherosclerosis genetic, environmental, and epigenetic factors are involved [4][5].…”

“…Genetic and epigenetic factors may be studied with two main approaches, candidate gene approach and genome wide association study (GWAS) approach [4][5][6][7][8][9]11]. Candidate gene approach is hypothesis-driven approach, whereas in GWAS approach appropriate subset of patients (i.e.…”

“…So far, several studies using either candidate gene approach or GWAS approach have been reported several genetic markers for either CIMT or subclinical carotid atherosclerosis, however most reports studied patients in general population, and only few enrolled subjects with type 2 diabetes mellitus (T2DM) [4][5][6][7][8][9]11]. It should be emphasized, however, that whatever approach (candidate gene or GWAS approach) may be used, crucial is well-designed and appropriately selected study group.…”