K469E Polymorphism Research Articles

Recent Progress in Genetics and Epigenetics Research on Diabetic Nephropathy in Malaysia.

Diabetic nephropathy is a multifactorial disease. Gene susceptibility, as well as environmental exposure, plays an important role in disease progression. Malaysia is reported to be among the world's second-fastest-growing rates of kidney failure. Diabetic nephropathy has become the main cause of end-stage renal disease in Malaysia. This article is aimed at reviewing genetic studies conducted among diabetic nephropathy patients in the Malaysian population. This review was conducted by searching PubMed, MEDLINE, and Google Scholar databases to identify all relevant papers published in English from March 2022 to April 2022, using the following keywords: diabetes, type 2 diabetes, diabetic nephropathy, diabetic kidney disease, and Malaysia. The case-control study among diabetic patients with and without diabetic nephropathy showed a significant association with diabetic nephropathy in CNDP1, NOS3, and MnSOD genes. In the ethnic subgroup analysis, significant differences for diabetic nephropathy in terms of diabetes duration (≥10 years) were observed for CCL2 rs3917887, CCR5 rs1799987, ELMO1 rs74130, and IL8 rs4073. The IL8 rs4073 was associated only with the Indians, while the CCR5 rs1799987 was associated with the Chinese. In Malays, SLC12A3 Arg913Gln polymorphism and ICAM1 K469E (A/G) polymorphism were found to be associated with diabetic nephropathy. Studies on gene-environment interactions have suggested significant genetic and environmental factors such as smoking, waist circumference, and sex for eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895, and KCNQ1 rs2283228 with kidney disease. The genetic variants' contributions differed across ethnic groups. Therefore, a study to validate the genetic variants that are found to be associated with different ethnicities in Malaysia may be important in future studies.

ICAM-1 and MKL-1 polymorphisms impose considerable impacts on coronary heart disease occurrence.

This study was aimed to explore the correlation of intercellular adhesion molecule‐1 (ICAM‐1) K469E and megakaryoblastic leukaemia factor‐1 (MKL‐1) −184C/T polymorphisms with the susceptibility to coronary heart disease (CHD) in the Chinese Han population. 100 CHD patients and 91 healthy people that had no blood connection with each other were enrolled in this case‐control study. ICAM‐1 and MKL‐1 polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) approach. Multiple logistic regression was used to analyse the correlation between polymorphisms of ICAM‐1 and MKL‐1 and CHD susceptibility. Differences of genotype and allele frequencies of the two SNPs between case and control groups were analysed by chi‐square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were indicated relative susceptibility of CHD. The distributions of ICAM‐1 and MKL‐1 polymorphisms in each group conformed to Hardy‐Weinberg equilibrium (HWE). After adjusting for traditional risk factors, the TT genotype frequency of MKL‐1 −184C/T polymorphism was found significantly higher in case group than in control group (P < .05). Meanwhile, T allele frequency increased in case group compared with control group, and the differences had statistical significance (P = .04, OR = 2.34, 95% CI = 1.34‐5.26). Logistic regression analysis in this study proved that smoking, hypertension, diabetes and triglyceride (TG) were all risk factors for CHD ICAM‐1 K469E polymorphism has no association with the onset of CHD. But MKL‐1 −184C/T polymorphism is associated with the risk of CHD and T allele might be a susceptibility factor for CHD.

Genetic and Biological Effects of ICAM-1 E469K Polymorphism in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a complex disease, in which local inflammatory stress results from both metabolic and hemodynamic derangements. Intercellular adhesion molecule 1 (ICAM-1) is an acute-phase protein marker of inflammation. In the recent years, clinical observations have reported that increased serum/plasma ICAM-1 levels are positively correlated with albuminuria in the patients with type 1 (T1D) and type 2 diabetes (T2D). Genetic association studies have demonstrated that genetic polymorphisms, including SNP rs5498 (E469K, G/A), in the ICAM1 gene is associated with DKD. rs5498 is a nonsynonymous SNP and caused by substitution between E (Glu) and K (Lys) for ICAM-1 protein. In this review, we first summarized the genetic effects of ICAM1 E469K polymorphism in DKD and then demonstrated the possible changes of ICAM-1 protein crystal structures according to the genotypes of this polymorphism. Finally, we discussed the genetic effects of the ICAM1 E469K polymorphism and the biological role of increased circulating ICAM-1 protein and its formation changes in DKD.

ICAM-1 promotes the abnormal endothelial cell phenotype in chronic thromboembolic pulmonary hypertension.

Pulmonary endothelial cells play a key role in the pathogenesis of Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Increased synthesis and/or the release of intercellular adhesion molecule-1 (ICAM-1) by pulmonary endothelial cells of patients with CTEPH has been recently reported, suggesting a potential role for ICAM-1 in CTEPH. We studied pulmonary endarterectomy specimens from 172 patients with CTEPH and pulmonary artery specimens from 97 controls undergoing lobectomy for low-stage cancer without metastasis. ICAM-1 was overexpressed in vitro in isolated and cultured endothelial cells from endarterectomy specimens. Endothelial cell growth and apoptosis resistance were significantly higher in CTEPH specimens than in the controls (p < 0.001). Both abnormalities were abolished by pharmacological inhibition of ICAM-1 synthesis or activity. The overexpression of ICAM-1 contributed to the acquisition and maintenance of abnormal EC growth and apoptosis resistance via the phosphorylation of SRC, p38 and ERK1/2 and the overproduction of survivin. Regarding the ICAM-1 E469K polymorphism, the KE heterozygote genotype was significantly more frequent in CTEPH than in the controls, but it was not associated with disease severity among patients with CTEPH. ICAM-1 contributes to maintaining the abnormal endothelial cell phenotype in CTEPH.

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

BackgroundThe intercellular adhesion molecule‐1 (ICAM‐1)/leukocyte function associated antigen‐1 (LFA‐1) adhesion system regulates leukocyte interactions, migration, and adhesion, and appears to play an important role in atherosclerosis and thrombosis. Therefore, single nucleotide polymorphisms (SNPs) of the ICAM‐1 gene may strongly influence the expression and biological activity of ICAM‐1 and play a potentially important role in the pathogenesis of ischemic stroke. In the current meta‐analysis, we investigated the relationship between the ICAM‐1 gene K469E SNP and the risk of ischemic stroke.MethodsTwo investigators independently searched PubMed, Web of Science, Google Scholar, WANFANG, China National Knowledge Infrastructure (CNKI) and J‐STAGE for studies published from January 2000 to February 2019 without language restriction. The association of K469E polymorphism and ischemic stroke in three genetic models (allelic, recessive, and dominant) were evaluated using Pooled odds ratios (ORs) with 95% confidence intervals (CIs).ResultsOur study included 20 studies from four continents and four different countries, including 3,137 cases and 15,382 controls. Meta‐analysis results did not show a significant association between K469E polymorphism of ICAM‐1 gene and ischemic stroke when assuming allelic model (OR: 1.12; 95% CI: 0.8 to 1.55; p = 0.51; I 2 = 93%) or recessive model (OR: 1.28; 95% CI: 0.89 to 1.84; p = 0.18; I 2 = 82%) or dominant model (OR: 1.20; 95% CI: 0.92 to 1.56; p = 0.17; I 2 = 85%). However, in all three genetic models, subgroup analysis revealed that the K469E polymorphism of the ICAM‐1 gene is associated with ischemic stroke in the Caucasian population.ConclusionK469E polymorphism of ICAM‐1 gene might be a risk factor for ischemic stroke in Caucasians, which suggested that K469E polymorphism might help in early identification of those at risk and help in primary prevention of ischemic stroke.

Association between the ICAM-1 gene polymorphism and coronary heart disease risk: a meta-analysis

Coronary heart disease (CHD) is a complex polygenic disease in which gene-environment interactions play a critical role in disease onset and progression. The Intercellular adhesion molecule 1 (ICAM-1) gene E469K polymorphism is one of the most commonly studied polymorphisms in this gene because of its association with CHD risks, but results were conflicting. The PubMed, Embase, and China National Knowledge Infrastructure databases were searched for case–control studies published up to November 2018. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the association. Eleven eligible studies, comprising 3435 cases and 3199 controls, were included in the meta-analysis. The pooled result showed that the ICAM-1 gene E469K polymorphism was significantly associated with an increased risk of CHD (OR = 1.20, 95% CI = 1.11–1.29, for the allele K versus allele E; OR = 1.66, 95% CI = 1.43–1.92, for the K allele carriers versus EE). Subgroup analysis supported the results in the Chinese populations and in the Caucasian populations. This meta-analysis suggests that the ICAM-1 gene K469E polymorphism is associated with CHD risk and the K allele is a more significant risk factor for developing CHD amongst Chinese and Caucasians populations.

Association between E469K polymorphism in the ICAM1 gene and the risk of diabetic nephropathy: a meta-analysis

BackgroundInflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN). Intercellular adhesion molecule 1 (ICAM1) is an acute phase marker of inflammation. ICAM1 rs5498 has been reported to be associated with the risk of DN. However, the previous findings were conflicting due to the limited sample sizes, different methodologies and ethnicities. Therefore, this study aimed to investigate the genetic association between ICAM1 rs5498 and the risk of DN.MethodsTwo investigators independently searched the studies from the databases PubMed, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Embase. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the associations.ResultsNo significant association was detected between ICAM1 rs5498 and DN susceptibility in allelic and recessive models (p > 0.05). However, significant reduction of frequencies of the dominant model of ICAM1 rs5498 was only detected in the Caucasian subgroup (OR = 0.80; 95% CI = [0.65, 0.99], p = 0.04) and type 1 diabetes mellitus subgroup (OR = 0.80; 95% CI = [0.65, 0.99], p = 0.04).ConclusionsThus, ICAM1 rs5498 might be a risk factor for DN in Caucasians and type 1 diabetes mellitus patients, which suggested that ICAM1 rs5498 might help in early diagnosis and prevention of this disease. Further studies were needed to clarify the biochemical function and pathological role of ICAM1 rs5498 in the risk of DN.

Coexistence of IL-6 -572C/G and ICAM-1 K469E Polymorphisms among Patients with Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSNHL) is a multifactorial disease, and its etiology remains elusive. SSNHL is possibly caused by both the environmental factors and genetic alterations. Recently, several studies suggested that inflammation may be involved in the pathogenesis of SSNHL, and certain gene polymorphisms may have correlations with SSNHL. Interleukin 6 (IL-6) functions both as a pro-inflammatory cytokine and an anti-inflammatory factor. Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin family that is also involved in inflammation response. Importantly, the IL-6 gene promoter contains a single nucleotide polymorphism (SNP), -572C/G, and ICAM-1 gene contains a SNP (A/G) in the protein-coding region, Lys (AAG)/Glu (GAG) at codon 469, known as K469E polymorphism. However, there is no study about the ICAM-1 gene polymorphism among SSNHL patients. In this study, we explored the relationship between SSNHL with IL-6 -572C/G and ICAM-1 K469E polymorphisms. We conducted a case-control study including 75 SSNHL patients and 165 healthy controls and analyzed the distribution and odds ratios of IL-6 and ICAM-1 genotypes. The frequency of the G allele at IL-6 -572C/G polymorphism was significantly higher among SSNHL patients than that among healthy individuals. In multivariate analysis, the coexistence of IL-6 -572G allele (GG/CG) and E allele (EE/KE) of ICAM-1 K469E polymorphism was significantly associated with an increased SSNHL risk (P < 0.001). In conclusion, we propose that the combination of IL-6 -572C/G and ICAM-1 K469E polymorphisms have a synergistic effect on the onset of SSNHL.

ICAM-1 K469E polymorphism, increased risk of neurocysticercosis occurrence and immunopathological defect.

Dear Editor, Neurocysticercosis is an important infectious neuropsychiatric disorder. The infection is caused by a parasite and is common in several tropical countries around the world. The role of immunity of the host for protection against neurocysticercosis is very interesting. The observation by Silva et al. on interleukin 4 (IL4) and neurocysticercosis is a good example. Here, we would like to draw more attention to a complex immunological defect that can underline increased risk for neurocysticercosis. We would like to [...]

Correlations of ICAM-1 gene polymorphisms with susceptibility and multidrug resistance in colorectal cancer in a Chinese population.

Background:Colorectal cancer (CRC) is a malignant gastrointestinal tumor with a high mortality rate, including both colon and rectal cancer. In order to provide clinical guidance for the treatment of CRC, this study is conducted to investigate the correlations of intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms with susceptibility and multidrug resistance (MDR) of colorectal cancer (CRC).Methods:A total of 195 patients with CRC were selected as the observation group and 188 healthy people enrolled as the control group. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to test ICAM-1 A13848G and K469E polymorphisms. The expressions of MDR-associated protein topoisomerase II (Topo II) and P-glycoprotein (P-gp) in CRC tissues were detected by immunohistochemistry. The analysis on association of clinical indexes of CRC patients with ICAM-1 gene polymorphisms was performed.Results:The frequencies of KK genotype and K allele of K469E in the observation group were significantly higher than that in the control group. KE + EE genotype and E allele might be protective factors for CRC. The distribution of genotypes, K469E KK and KE+EE, was highly correlated with histologic grade of tumor differentiation. Compared with adjacent normal tissues, positive rates of Topo II and P-gp expression were significantly increased in CRC tissues. Topo II expression in CRC patients was positively associated with lymph node metastasis and depth of tumor invasion, whereas P-gp expression was only associated with depth of tumor invasion. Higher positive rates of Topo II and P-gp expression were observed in ICAM-1 K469E KK genotype carriers, indicating that ICAM-1 K469E KK genotype might be related to MDR in CRC.Conclusion:These findings in the current study suggested that ICAM-1 K469E polymorphism is highly correlated with susceptibility and MDR in CRC.

Serum ICAM-1 level and ICAM-1 gene 1462A>G (K469E) polimorphism on microalbuminuria in nondiabetic, nonhypertensive and normolipidemic obese patients: Genetical background of microalbuminuria in obesity

BackgroundA growing body of evidence suggest that obese individuals are under risk of renal parenchymal disorders when compared to nonobese counterparts. Microalbuminuria is the early marker of renal involvement. Although most of obese patients carries multiple risk factors for microalbuminuria, some obese individuals without risk factor may progress to microalbuminuria. The present study was performed to examine the role of ICAM-1 gene 1462A>G (K469E) polymorphism on microalbuminuria in obese subjects without diabetes mellitus, hypertension, hiperlipidemia and older age. MethodsNinety eight obese and 96 nonobese individuals without a comorbidity enrolled into the study. Serum ICAM-1 level was measured by enzyme linked immunoabsorbent assay (ELISA) method. ICAM-1 gene 1462A>G (K469E) polymorphism was examined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Nepholometric method was used to examine urinary albumin loss, and microalbuminuria was measured by albumin to creatinine ratio. ResultsObese individuals had significantly higher microalbuminuria and proteinuria level compared to nonobese subjects (p: 0.043 and p: 0.011; respectively). GG genotype of ICAM-1 carriers have significantly higher microalbuminuria compared to individuals with AA or AG genotype carriers (p: 0.042). Serum ICAM-1 level was significantly correlated with creatinine and microalbuminuria (p: 0.002 and p: 0.03; respectively). Logistic regression analysis indicated a 7.39 fold increased risk of microalbuminuria in individuals with GG genotype of ICAM-1 gene 1462A>G (K469E) polymorphism. ConclusionsGG genotype of ICAM-1 gene K469E polymorphism is associated with increased microalbuminuria in obese individuals without another metabolic risk factor.

Serum ICAM-1 level and ICAM-1 gene 1462A>G (K469E) polimorphism on microalbuminuria in nondiabetic, nonhypertensive and normolipidemic obese patients: Genetical background of microalbuminuria in obesity

BackgroundA growing body of evidence suggest that obese individuals are under risk of renal parenchymal disorders when compared to nonobese counterparts. Microalbuminuria is the early marker of renal involvement. Although most of obese patients carries multiple risk factors for microalbuminuria, some obese individuals without risk factor may progress to microalbuminuria. The present study was performed to examine the role of ICAM-1 gene 1462A>G (K469E) polymorphism on microalbuminuria in obese subjects without diabetes mellitus, hypertension, hiperlipidemia and older age. MethodsNinety eight obese and 96 nonobese individuals without a comorbidity enrolled into the study. Serum ICAM-1 level was measured by enzyme linked immunoabsorbent assay (ELISA) method. ICAM-1 gene 1462A>G (K469E) polymorphism was examined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Nepholometric method was used to examine urinary albumin loss, and microalbuminuria was measured by albumin to creatinine ratio. ResultsObese individuals had significantly higher microalbuminuria and proteinuria level compared to nonobese subjects (p: 0.043 and p: 0.011; respectively). GG genotype of ICAM-1 carriers have significantly higher microalbuminuria compared to individuals with AA or AG genotype carriers (p: 0.042). Serum ICAM-1 level was significantly correlated with creatinine and microalbuminuria (p: 0.002 and p: 0.03; respectively). Logistic regression analysis indicated a 7.39 fold increased risk of microalbuminuria in individuals with GG genotype of ICAM-1 gene 1462A>G (K469E) polymorphism. ConclusionsGG genotype of ICAM-1 gene K469E polymorphism is associated with increased microalbuminuria in obese individuals without another metabolic risk factor.

The Lys469glu/K469E Polymorphism of the Inflammatory Gene Intercellular Adhesion Molecule-1 Lacks any Apparent Role in the Polycystic Ovary Syndrome in Kashmiri Women: A Case Control Study

Background:Polycystic ovary syndrome (PCOS), associated with a state of low grade chronic inflammation, depends on multiple genetic and environmental factors. Elevated levels of inflammatory markers including intercellular adhesion molecule-1 (ICAM-1) have been demonstrated in affected women. Recent evidence indicates a significant linkage between chromosome 19p13 loci and multifactorial diseases that have an inflammatory component. The aim of this study was to assess the possible association of the lys469glu (K469E) polymorphism of the ICAM-1 gene located on chromosome 19p13 with risk of PCOS in Kashmiri women.Material and Methods:The K469E single nucleotide polymorphism (SNP) was analysed with DNA from peripheral blood leukocytes of 220 PCOS cases and 220 age matched non-PCOS healthy controls using PCR-RFLP.Results:Genotypic frequencies in cases were found to be 32 (14.5%) for EE, 98 (44.5%) for KE, and 90 (40.9%) for KK, with 130 (59.1%) for the KE+EE genotypes compared to healthy control values of 29 (13.2%) for EE, 113 (51.4%) for KE, 78 (35. 5%) for KK and 142 (64.5%) for KE+EE combined. The odds ratios for the EE,KE and KE:EE genotypes were 0.95(95% CI= 0.53-1.71)[p= 0.88], 0.75(95% CI= 0.50-1.12)[p =0.168] and 0.79 (95% CI =0.53-1.16) [p = 0.23], no statistically significant differences being found between cases and controls (χ2 =2.07; p=0.35).Conclusion:In conclusion, there was no apparent significant influence of the K469E polymorphism on risk of PCOS, or any clinical or laboratory parameters.

Possible lack of association between E469K polymorphism of ICAM-1 and non-obstructive azoospermia in south-east Turkey

ABSTRACTIntercellular adhesion molecule-1 (ICAM-1), a member of the large immunoglobulin superfamily of cell adhesion molecules, is a constituent component of the blood–testis barrier, and it plays a significant role in the homeostasis of spermatogenesis. The E469K polymorphism in the human ICAM-1 gene has been previously associated in various inflammatory/autoimmune disorders. However, the role of the ICAM-1 E469K polymorphism in spermatogenesis remains unclear. The aim of the present study is to analyse the possible association between the ICAM-1 E469K polymorphism and male infertility with non-obstructive azoospermia (NOA) patients within a group of men from Turkey. We included 111 infertile male with NOA and 114 fertile male as control subjects to the study. Genotyping was made by polymerase chain reaction–restriction fragment length polymorphism. The frequency of the genotype and the allele of ICAM-1 E469K were not significantly different between the control group and the patients (P > 0.05). This is the first study to investigate the role of the ICAM-1 gene polymorphism in male infertility with NOA. We conclude that the E469K polymorphism of ICAM-1 is not a risk factor for NOA in the Turkish population.

P16 INTERCELLULAR ADHESION MOLECULE-1 K469E(A/G) POLYMORPHISM AND ITS EFFECTS IN THE DEVELOPMENT OF DIABETIC NEPHROPATHY

Recent research has implicated that inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN), although its pathogenesis is multifactorial. Intercellular adhesion molecule 1 (ICAM-1) is an acute phase marker of inflammation and the ICAM-1 gene is located on chromosome 19p13.2 and resides a linkage region to diabetes and DN. To investigate whether ICAM-1 has effects in the development of DN, we have recently performed genetic and pathological studies of this molecule in Swedish and Malaysian subjects with normal glucose tolerance (NGT), diabetes and DN. We genotyped six single nucleotide polymorphisms (SNPs) in the ICAM-1 gene with TaqMan allelic discrimination. We also determined plasma ICAM-1 levels with an enzyme-linked immune-sorbent assay kit. We found that non-synonymous SNP rs5498 (K469E A/G) was associated diabetes and DN and the G allele had a protective effect. Particularly, we found a high heterozygous index of this polymorphism presenting in both populations. The genotype distribution of this polymorphism was kept in Hardy-Weinberg Equilibrium and no duplicon in the genomic sequence was found. The ICAM-1 K469E(A/G) polymorphism resides in the 5th Ig-like domain of ICAM-1 protein. This domain is essential for dimerization, surface presentation and solubilisation of proteins of the protein and subsequently plays a crucial role in the activity of ICAM-1 protein in the interaction with LFA-1 and the adhesion of B cells. Furthermore, we found the carriers with heterozygous genotype had higher fasting glucose levels among newly diagnosed type 2 diabetes patients compared with the subjects with wild or mutant homozygous genotype. Plasma ICAM-1 levels were increased from the subjects with NGT, diabetes without DN to the patients with DN. Among diabetic patients with DN, the carriers with heterozygous genotype had higher plasma ICAM-1 levels compared with other patients. Our study provided evidence that ICAM-1 has effects in the development of DN. The patients carrying with heterozygous genotype of SNP rs5498 (K469E A/G) in the ICAM-1 gene have higher risk susceptibility to DN. The combined approach with genotyping this polymorphism and measuring plasma ICAM-1 levels may be useful for prediction of DN in translation medicine.

Intercellular adhesion molecule-1 polymorphisms, K469E and G261R and susceptibility to vasculitis and rheumatoid arthritis: a meta-analysis.

The aim of this study was to determine whether intercellular adhesion molecule-1 (ICAM-1) polymorphisms are associated with susceptibility to vasculitis or rheumatoid arthritis (RA). Meta-analyses were performed to assess the associations between K469E and G241R polymorphisms of ICAM-1 and vasculitis or RA. A total of 12 studies on 1,368 patients and 1,922 controls, which comprised 8 vasculitis studies and 4 RA studies, were included in the meta-analysis. We found no significant association between vasculitis and K469E E allele among the various subjects (OR = 1.238, 95% CI = 0.9781-1.566, p = 0.076). However, an association between vasculitis and K469E polymorphism was observed under homozygote contrast (OR = 1.443, 95% CI = 1.084-1.920, p = 0.012). Stratification by ethnicity and vasculitis type showed no association between vasculitis and 1 K469E polymorphism under heterozygote contrast. In addition, the meta-analysis revealed a significant association between the ICAM-1 G241R R allele and Behcet's disease (BD) (OR = 3.261, 95% CI = 1.653-6.434, p = 0.001), but not giant cell arteritis. Moreover, the meta-analysis indicated an association between RA and the R allele and RR+ RG genotype of the ICAM-1 G241R polymorphism (OR = 2.014, 95% CI = 1.215-3.339, p = 0.007; OR = 2.394, 95% CI = 1.354-4.235, p = 0.003). This meta-analysis suggests that the K469E polymorphism is associated with susceptibility to vasculitis, and that the G241R polymorphism is associated with susceptibility to BD and RA.

Polymorphisms of ICAM-1 and IL-6 genes related to endometriosis in a sample of Brazilian women.

This study investigated the possibility of K469E (rs5498) and G241R (rs1799969) polymorphisms, in ICAM-1 gene, and G634C (rs1800796), in IL-6 gene, being associated with the occurrence of endometriosis in a sample of Brazilian women. We genotyped 200 women (100 in control group and 100 in endometriosis group) by PCR-RFLP technique for G634C, K469E, and G241R polymorphisms. No significant difference was observed in genotypic frequency between control and endometriosis groups for G634C and K469E polymorphisms (p = 0.61 and p = 0.22, respectively). In addition, no significant difference between stages I-II and III-IV of the disease was found for both SNPs (p = 0.63 and p = 0.24, respectively). All individuals were wild homozygotes for G241R polymorphism. This study suggests that polymorphisms K469E, G241R, and G634C are not associated with increased susceptibility to endometriosis in Brazilian women.

Association of ICAM-1 K469E polymorphism with dengue infection in North Indian population

Dengue infection is caused by flavivirus is one of the leading cause of mortality. There are certain factors which play role in the transformation of a mild form of the disease (DF) into a severe form (DHF) but the most important ones are: viral strain virulence, host genetics, and host immune status. In severe dengue infection, plasma leakage occurs due to vascular endothelial cell activation through expression of adhesion molecule like intercellular cell adhesion molecule-1 (ICAM-1). A total of 100 dengue patients (DF; n = 53 and DHF/DSS; n = 47) and 200 healthy controls were included in the study. ICAM-1 K469E genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). Expression of ICAM-1 mRNA was done by Real time reverse transcription- PCR (rRT-PCR). Patients with homozygous genotype (EE) have 3.22 fold risk (P = 0.008) of developing severe form of disease (DHF/DSS) as compared to other genotypes. Patients with DHF/DSS exhibit higher expression of ICAM-1 mRNA as compared to dengue fever and controls (P = 0.001 and < 0.001). Patients (DHF/DSS) with homozygous (EE) genotype exhibit higher expression of ICAM-1 mRNA when compared with wild type (KK) genotype (P = 0.005). This study suggests a possible association between the ICAM-1 polymorphism and the disease severity.

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

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 two single base polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease.

The present study evaluated the association between G241R and K469E polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease in Iranian population. Inflammatory bowel disease including ulcerative colitis and Crohn's disease, is a chronic idiopathic inflammatory disease of the gastrointestinal tract. There are two single base polymorphisms of intercellular adhesion molecule 1gene, G241R and K469E, reported to be associated with inflammatory disorders. In this case-control study, 156 inflammatory bowel disease patients (110 ulcerative colitis and 46 Crohn's disease patients) and 131 healthy controls were enrolled. Two polymorphisms of intercellular adhesion molecule 1 gene, including G241R and K469E, were assessed by polymerase chain reaction followed by restriction fragment length polymorphism. The E469 allele of K469E polymorphism was significantly more frequent in Crohn's disease patients compared to controls (P< 0.05, OR= 1.83; 95% CI: 1.13 to 2.96). The mutant homozygote genotype of K469E polymorphism (E/E) was also significantly more frequent in Crohn's disease patients compared to controls (P< 0.05, OR= 4.23; 95% CI: 1.42 to 12.59). No difference was observed in the frequency of K469E polymorphism among ulcerative colitis patients compared to controls. There were no significant differences in genotype and allele frequencies of G241R polymorphism among ulcerative colitis and Crohn's disease patients compared to control subjects. According to our findings, K469E polymorphism of intercellular adhesion molecule 1 gene may probably participate in the pathogenesis of Crohn's disease in Iran.