Dataset Information

Association between NF-?B 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-?B (NF-?B) 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-?B 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-?B 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.

SUBMITTER: Wu S

PROVIDER: S-EPMC5240939 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Wu Semon S Teng Ming-Sheng MS Er Leay-Kiaw LK Hsiao Wan-Yi WY Hsu Lung-An LA Yeh Ching-Hua CH Lin Jeng-Feng JF Lin Yi-Ying YY Su Cheng-Wen CW Ko Yu-Lin YL

PloS one 20170117 1

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 ...[more]

PMID: 28095483

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Project description:The TBX5 gene, a member of the T-box family, is associated with congenital heart disease, electrocardiographic parameters, and development of atrial fibrillation in the general population. This study aimed to elucidate the role of TBX5 gene polymorphisms in metabolic and inflammatory profiles possibly linked to TBX5-related pathologies.A sample population of 597 individuals having routine health examinations was enrolled. Five tagging TBX5 single nucleotide polymorphisms (SNPs) were analyzed using polymerase chain reaction and restriction enzyme digestion or TaqMan SNP genotyping assays. Associations between genotypes/haplotypes and matrix metalloproteinase 9 (MMP9) levels were investigated using generalized linear model analysis. Interactions between each genotype/haplotype, MMP9 level, and obesity status were tested using two-way analysis of variance with Golden Helix SVS Win32 7.3.1 software.After adjusting for clinical covariates, TBX5 genotypes were found to be associated with MMP9 levels (p = 0.002 and p = 0.001 for rs4113925 and rs3825214, respectively) in a dominant inheritance model. Haplotype analysis using three tag SNPs (rs11067101, rs1247973, and rs3825214) revealed a significant association between TBX5 haplotype GCG and MMP9 levels (uncorrected p = 0.0093 and the corrected false discovery rate p = 0.0435). Multivariate analysis identified that SNP rs3825214, in addition to the MMP9 and E-selectin genotypes, was independently associated with MMP9 levels (p < 0.001). Using a dominant inheritance model, subgroup and interaction analysis showed associations between the rs4113925, rs3825214, and MMP9 levels only in nonobese individuals (p = 1.04 × 10-4 and p = 7.11 × 10-5, respectively; interaction p = 0.009 and 0.018, respectively). Subgroup analysis showed a borderline significant association between haplotype GCG and MMP9 levels (uncorrected p = 0.020 and corrected false discovery rate p = 0.073), but with no evidence of interaction.TBX5 genotypes/haplotypes are independently associated with MMP9 in Taiwanese individuals and occur predominantly in nonobese people. These associations may broaden our understanding of the mechanism underlying T-box family gene activity and related cardiovascular pathologies.

Project description:BackgroundHepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses.MethodsA total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies.ResultsSNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01).ConclusionOur data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.

Dataset Information

Association between NF-?B Pathway Gene Variants and sICAM1 Levels in Taiwanese.

Publications

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

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