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IL1B genetic variation and plasma C-reactive protein level among young adults: the CARDIA study.

ABSTRACT: Interleukin-1B (IL1B) modulates C-reactive protein (CRP) expression. However, whether IL1B genetic variation is associated with CRP level is unknown. Further, obesity, a state of low-grade inflammation that influences cellular IL-1 functions may modify this association.Study participants (N=3289), 48% blacks and 52% whites, had CRP level measurements at year 7 and year 15 examinations as part of the CARDIA study. Ten tag single nucleotide polymorphisms (SNPs) that characterize common IL1B gene variation were genotyped. In SNP analysis, no significant associations with either level or change in time CRP were observed after multiple testing adjustments. However, global ILIB gene variation was associated with year 7 to year 15 change in CRP (global nominal p=0.004, multiple testing corrected p=0.048) among obese blacks. Compared to the commonest haplotype, a common haplotype that includes the SNP rs1143642 was associated with greater increases in CRP from year 7 to year 15 among obese blacks and whites while another common haplotype that includes the SNP rs3917356 was associated with decreased change in CRP from year 7 to year 15 among obese blacks. The rare alleles of ILIB SNPs, SNP 7114 (rs1143642) and SNP 3298 (rs3917356), were associated with greater increases and decreases in CRP from year 7 to year 15 among blacks, respectively, compared to their common variants.IL1B genetic variation may have a role in CRP level regulation and this association may be modified by obesity.

SUBMITTER: Enquobahrie DA

PROVIDER: S-EPMC2847778 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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IL1B genetic variation and plasma C-reactive protein level among young adults: the CARDIA study.

Enquobahrie Daniel A DA Rice Kenneth K Williams O Dale OD Williams Michelle A MA Gross Myron D MD Lewis Cora E CE Schwartz Stephen M SM Siscovick David S DS

Atherosclerosis 20080518 2

<h4>Objective</h4>Interleukin-1B (IL1B) modulates C-reactive protein (CRP) expression. However, whether IL1B genetic variation is associated with CRP level is unknown. Further, obesity, a state of low-grade inflammation that influences cellular IL-1 functions may modify this association.<h4>Methods and results</h4>Study participants (N=3289), 48% blacks and 52% whites, had CRP level measurements at year 7 and year 15 examinations as part of the CARDIA study. Ten tag single nucleotide polymorphis ...[more]

PMID: 18573495

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Project description:Proteins, widely studied as potential biomarkers, play important roles in numerous physiological functions and diseases. Genetic variation may modulate corresponding protein levels and point to the role of these variants in disease pathophysiology. Effects of individual single nucleotide polymorphisms (SNPs) within a gene were analyzed for corresponding plasma protein levels using genome-wide association study (GWAS) genotype data and proteomic panel data with 132 quality-controlled analytes from 521 Caucasian participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Linear regression analysis detected 112 significant (Bonferroni threshold p=2.44×10(-5)) associations between 27 analytes and 112 SNPs. 107 out of these 112 associations were tested in the Indiana Memory and Aging Study (IMAS) cohort for replication and 50 associations were replicated at uncorrected p<0.05 in the same direction of effect as those in the ADNI. We identified multiple novel associations including the association of rs7517126 with plasma complement factor H-related protein 1 (CFHR1) level at p<1.46×10(-60), accounting for 40 percent of total variation of the protein level. We serendipitously found the association of rs6677604 with the same protein at p<9.29×10(-112). Although these two SNPs were not in the strong linkage disequilibrium, 61 percent of total variation of CFHR1 was accounted for by rs6677604 without additional variation by rs7517126 when both SNPs were tested together. 78 other SNP-protein associations in the ADNI sample exceeded genome-wide significance (5×10(-8)). Our results confirmed previously identified gene-protein associations for interleukin-6 receptor, chemokine CC-4, angiotensin-converting enzyme, and angiotensinogen, although the direction of effect was reversed in some cases. This study is among the first analyses of gene-protein product relationships integrating multiplex-panel proteomics and targeted genes extracted from a GWAS array. With intensive searches taking place for proteomic biomarkers for many diseases, the role of genetic variation takes on new importance and should be considered in interpretation of proteomic results.

Dataset Information

IL1B genetic variation and plasma C-reactive protein level among young adults: the CARDIA study.

Publications

IL1B genetic variation and plasma C-reactive protein level among young adults: the CARDIA study.

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