Lack of Association Between Genetic Variation in 9 Innate Immunity Genes and Baseline CRP Levels.

Area of Science:

• Immunogenetics
• Cardiovascular Disease Risk Factors

Background:

• Baseline C-reactive protein (CRP) levels are an established independent risk factor for cardiovascular disease.
• Genetic factors influencing CRP levels are hypothesized to reside within the innate immunity system.

Purpose of the Study:

• To investigate the association between common single nucleotide polymorphisms (SNPs) in nine innate immunity genes and C-reactive protein (CRP) levels.
• To determine if genetic variations in CARD15, IRAK1, IRAK4, LBP, LY86, MEFV, TLR2, TLR4, and NFKB1 influence CRP levels.

Main Methods:

• Candidate gene association study design.
• Analysis of 63 common, linkage disequilibrium (LD)-independent SNPs in 717 women from the Women's Health Study with extreme CRP levels (low <0.2 mg/liter, high >5 mg/liter).
• Inclusion of specific non-synonymous SNPs in TLR4 and CARD15.

Main Results:

• Univariate, haplotype, and gene-gene interaction analyses revealed no significant association between common SNPs in the studied innate immunity genes and CRP levels.
• This study excludes a significant role for common variants in these nine genes in determining CRP levels.

Conclusions:

• Common genetic variations in the investigated innate immunity genes do not significantly impact C-reactive protein levels.
• Rarer genetic variants or variations in other innate immunity genes may still influence CRP levels and cardiovascular risk.