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


CONCLUSIONS
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.
Paik
Jean Kyung
JK
Clinical Nutrigenetics/Nutrigenomics Lab, Department of Food & Nutrition, College of Human Ecology, Yonsei University, Seoul, Republic of Korea.
Kim
Oh Yoen
OY
Koh
Soo Jeong
SJ
Jang
Yangsoo
Y
Chae
Jey Sook
JS
Kim
Ji Young
JY
Kim
Hyae Jin
HJ
Hyun
Yae Jung
YJ
Cho
Jung Rae
JR
Lee
Jong Ho
JH
D000328:Adult; D000886:Anthropometry; D015415:Biomarkers / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001827:Body Height / Q000502:physiology; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D015415:Biomarkers; D001786:Blood Glucose; D015850:Interleukin-6; D008055:Lipids; D002097:C-Reactive Protein