Association between NF-κB Pathway Gene Variants and sICAM1 Levels in Taiwanese

Abstract

Intercellular adhesion molecule–1 (ICAM1) is crucial to the development and progression of atherosclerosis. Recent genome-wide association studies (GWAS) have revealed that single nucleotide polymorphisms (SNPs) in two of the nuclear factor-κB (NF-κB) pathway genes, NFKBIK and RELA, are associated with soluble ICAM1 (sICAM1) levels. However, neither of these two gene variants is found in the Asian populations. This study aimed to elucidate whether other candidate gene variants involved in the NF-κB pathway may be associated with sICAM1 levels in Taiwanese. After excluding carriers of the ICAM1 rs5491-T allele, three SNPs in the ICAM1 gene and eight SNPs in six of the NF-κB pathway genes (NFKB1, PDCD11, TNFAIP3, NKAPL, IKBKE, and PRKCB) were analyzed for their association with sICAM1 levels in 480 individuals. Our data showed that two SNPs, rs5498 of ICAM1 and rs1635 of NKAPL, were significantly associated with sICAM1 levels (P = 0.002 and 0.004, respectively) in the Taiwanese population. Using a multivariate analysis, rs5498 and rs1635 as well as the previously reported ABO genotypes and rs12051272 of the CDH13 gene were independently associated with sICAM1 levels (P = 0.001, 0.001, 0.006 and 0.031, respectively). An analysis with combined risk alleles of four candidate SNPs in the ICAM1, NKAPL, ABO, and CDH13 genes showed an increase in sICAM1 levels with added numbers of risk alleles and weighted genetic risk score. Our findings thus expanded the repertoire of gene variants responsible for the regulation of sICAM1 levels in the Asian populations.

Genetic Variation in Human Gene Regulatory Factors Uncovers Regulatory Roles in Local Adaptation and Disease

“…2015), and performs other functions that can alter the neurological processes in the brain. This scenario is in line with the results obtained by Wu et al. (2017), who suggested that NKAPL rs1635 (T152N mutation) may be related to central nervous system development and significantly associated with the plasma levels of Intercellular adhesion molecule–1 (sICAM1), an important cell adhesion molecule with essential roles in inflammatory processes.…”

Endothelial cells of pulmonary origin display unique sensitivity to the bacterial endotoxin lipopolysaccharide

“…Interestingly, we found that silencing pulmonary HMVEC‐CDH13 significantly decreased whole cell ICAM‐1 and demonstrated a decreased ICAM‐1 surface expression in the PBS‐treated group and a decreased trend in the LPS‐treated group. A Genome‐Wide Association Study in the Taiwanese population showed an association between CDH13 risk alleles and increased soluble ICAM‐1 (Wu et al, 2017 ), supporting a mechanistic interaction between CDH13 and ICAM‐1 expression. CDH13 has also been shown to be elevated in early atherosclerosis (Philippova et al, 2011 ), and ICAM‐1 has been found to be crucial for the development of atherosclerosis (Lawson & Wolf, 2009 ; Wu et al, 2017 ).…”

Anti-inflammatory effects of powdered product of Bu Yang Huan Wu decoction: Possible role in protecting against Transient Focal Cerebral Ischemia

“…While most studies including the present one examine the acute effects of BYHW on stroke, the effects of chronic treatment of BYHW are yet to be fully elucidated. Long-term effects of BYHW on suspected genes or target proteins related to inflammation and mitochondria homeostasis in ischemic stroke and peripheral artery diseases also warrant further research [9,26,27,28].…”