Additive effect of interleukin-6 and C-reactive protein (CRP) single nucleotide polymorphism on serum CRP concentration and other cardiovascular risk factors

Autor: Soo Jeong Koh, Jong Ho Lee, Hyae Jin Kim, Jey Sook Chae, Ji-Young Kim, Yae Jung Hyun, Jean Kyung Paik, Oh Yoen Kim, Yangsoo Jang, Jung Rae Cho
Rok vydání: 2007
Předmět:
Zdroj: Clinica Chimica Acta. 380:68-74
ISSN: 0009-8981
DOI: 10.1016/j.cca.2006.11.011
Popis: Background Serum C-reactive protein (CRP) levels, closely associated with cardiovascular disease (CVD) risk are influenced by CRP or interleukin-6 (IL-6) single nucleotide polymorphism (SNPs). However, it is still controversial. Therefore, we investigated the association of IL-6/CRP SNPs and serum CRP levels or other CVD risk factors in healthy adult Korean men. Methods In healthy adult men (age ≥ 20 years, n = 677), we genotyped IL-6−572C > G and CRP SNPs (− 717G > A, 1444C > T, 2147A > G) and measured anthropometric parameters, lipid profile, serum levels of CRP and IL-6 and insulin resistance. Results At IL-6−572C > G (n = 677), subjects with G/G genotype (n = 42) showed higher concentrations of CRP (P = 0.027) and IL-6 (P = 0.028) as compared with C allele carriers after age-adjustment (C/C: n = 371, C/G: n = 264). Fasting insulin and homeostatis model assessment insulin resistance (HOMA-IR) were also higher in G/G genotype. However, there were no significant differences in other metabolic biomarkers. Among 677 study subjects, 676 were genotyped at CRP−717G > A (G/G: n = 513, G/A: n = 150, A/A: n = 13), 672 at CRP+1444C > T (C/C: n = 580, C/T: n = 85, T/T: n = 7), and 668 at CRP+2147A > G (A/A: n = 273, A/G: n = 296, G/G: n = 99). There were no significant differences in CRP concentrations and other markers related to CVD risk according to each CRP SNP genotype. However, we could find the additive gene–gene interaction between IL-6−572C > G and CRP SNPs on CRP concentration; subjects with the ‘G/G’ at IL-6−572 showed the highest CRP levels when they have variant allele at CRP SNPs after adjusted for age, body mass index, cigarette smoking and alcohol drinking (− 717G > A: F = 7.806, P = 0.005; CRP + 1444C > T: F = 8.398, P = 0.004; and CRP + 2147A > G: F = 7.564, P = 0.006, respectively) Particularly, G allele carriers at CRP+2147A > G in subjects with IL-6−572G/G showed highest HOMA-IR (F = 9.092, P = 0.003). Conclusion The present data showed that serum CRP levels and other CVD risk factors appeared more influenced by IL-6−572C > G rather than CRP SNPs (− 717G > A, 1444C > T, and 2147A > G), however CRP levels and insulin resistance may be additively affected by IL-6−572 and CRP SNP, particularly when subjects with G/G genotype at IL-6−572 have allele variant at CRP SNPs.
Databáze: OpenAIRE
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