title: 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.
authors.affiliation: Department of Life Science, Chinese Culture University, Taipei, Taiwan.|Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
authors.forename: Semon
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: Teng
authors.affiliation: The Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
authors.forename: Leay-Kiaw
authors.initials: LK
authors.lastname: Er
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
authors.forename: Wan-Yi
authors.initials: WY
authors.lastname: Hsiao
authors.affiliation: The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Lung-An
authors.initials: LA
authors.lastname: Hsu
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine and, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Yeh
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine and, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
authors.forename: Jeng-Feng
authors.initials: JF
authors.lastname: Lin
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine and, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Su
authors.affiliation: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.|Cardiovascular Center and Division of Cardiology, Department of Internal Medicine and, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei city, Taiwan.|School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Ko
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D056970:Co-Repressor Proteins / Q000235:genetics*; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D056970:Co-Repressor Proteins; C573420:ICAM1 protein, human; D016328:NF-kappa B; C569368:NKAPL protein, human; D009687:Nuclear Proteins; D018799:Intercellular Adhesion Molecule-1