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

PLoS One. 2017 Jan 17;12(1):e0169516. doi: 10.1371/journal.pone.0169516. eCollection 2017.

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.

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Co-Repressor Proteins / genetics*
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / genetics*
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / blood*
  • Intercellular Adhesion Molecule-1 / genetics*
  • Male
  • Middle Aged
  • NF-kappa B / genetics*
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Taiwan / epidemiology

Substances

  • Biomarkers
  • Co-Repressor Proteins
  • ICAM1 protein, human
  • NF-kappa B
  • NKAPL protein, human
  • Nuclear Proteins
  • Intercellular Adhesion Molecule-1

Grants and funding

This study was supported by a grant from the Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-103-RT-2, TCRD-I103-01-01, TCRD-TPE-NCS-102-01, TCRD-TPE-MOST-103-01, TCRD-TPE-MOST-104-09), a grant from the Tzu Chi University, Hualien, Taiwan (TCIRP102001-02Y1, TCMMP104-06-03), and a grant from the National Science Council (NSC 101-2314-B-303 -023 -MY3, MOST 104-2314-B-303-013-MY3) to Y.-L. Ko and a grant from the Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-102-3, TCRD-TPE-103-22) to M.-S. Teng. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.