Plasma levels of fibrinogen and C-reactive protein are related to interleukin-6 gene −572C>G polymorphism in subjects with and without hypertension

Abstract

Hypertension is an important risk factor for cardiovascular diseases. There is increasing evidence suggesting that inflammation is involved in the development of hypertension. Interleukin-6 (IL-6) is an important mediator of inflammatory response and the major regulator of hepatic production of acute phase proteins, such as fibrinogen and C-reactive protein (CRP), which have been associated with hypertension and cardiovascular diseases. Therefore, we studied the association of single nucleotide polymorphism (SNP) in the IL-6 gene (IL6) promoter with plasma levels of fibrinogen, CRP and hypertension. Five hundred and two Hong Kong Chinese subjects (282 normotensives and 220 hypertensives) were recruited. IL-6 gene promoter was examined for polymorphism and the study subjects were genotyped for any SNP identified. The IL6 À572C4G polymorphism (rs1800796) was found with a frequency of 0.23 for the minor G allele. Subjects with the À572G allele had significantly higher plasma fibrinogen (3.0670.57 vs 2.8370.60, P ¼ 0.002) and CRP (interquartile range 0.33-1.56 vs 0.12-0.93, P ¼ 0.003) levels than those without. The À572C4G polymorphism was found to be an independent predictor of fibrinogen and CRP levels after adjusting for confounding factors. Plasma concentrations of fibrinogen and CRP correlated with systolic blood pressure. However, the À572C/G genotype frequencies did not differ between hypertensive and normotensive subjects, and there was no association between À572C4G polymorphism and blood pressure. Our results provide evidence that there is a clear genetic influence of IL6 À572C4G polymorphism on plasma levels of fibrinogen and CRP, but this polymorphism does not lead to elevated blood pressure.

Investigation of relationship between IL-6 gene variants and hypertension in Turkish population

“…In accordance to our findings, no significant differences were found between IL-6 -174 G/C and -572 G/C polymorphisms and HT whereas some other studies showed relations between IL-6 -174 G/C polymorphism and HT and also cardiovascular diseases (CVD) (Humphries et al 2001;Timasheva et al 2008;Losito et al 2003;Pola et al 2002;Wong et al 2007). …”

“…Polymorphisms -174 G/C and -572 G/C were shown to be associated with plasma IL-6 (Humphries et al 2001;Fishman et al 1998;Losito et al 2003) and CRP levels (Humphries et al 2001;Losito et al 2003;Wong et al 2007).…”

“…IL-6 stimulates release of acute phase reactants such as CRP, fibrinogen, amyloid A, TNF-a and IL-ip. It is known that elevated CRP blood levels enhanced hypertension development by inflammation (Wong et al 2007;Savoia and Schiffrin 2006).…”

Interleukin-6 -634C>G polymorphism in hypertensive patients with and without left ventricular hypertrophy

“…The negative results could be explained in a number of ways. First, EH is not a single entity; rather, it is likely to result from the interaction between environmental factors and a genetic predisposition to many polygenic quantitative traits acting in concert in various combinations in different individuals (26). The contribution of the -634c>g polymorphism to EH may therefore be so small that our study simply lacked the power to detect it.…”

Implications of Genetic Polymorphisms in Inflammation-Induced Atherosclerosis

“…After adjusting for covariates and post-hoc analysis, only rs3091244 SNP was associated with prevalent CAD, particularly in the non-Hispanic White population [46]. In a more recent analysis of data pooled from 5 different studies comprising of 4610 CAD patients and over CIMT [32] High CRP levels [22,52,53,55] PAD [33] High Systolic Blood pressure [27] Increased arterial stiffness [28] Insulin insensitivity [84] Lipid abnormalities [34] -572G>C rs1800796 CAD / MI [38] High plasma IL6 levels [24] Plasma IL6, CRP, Fibrinogen [54] CRP +1444C>T rs3091244 CAD [46] High plasma CRP levels [42,45,52,85,86] Stroke [87] Hypertension [47] Obesity [50] rs3093058 High Plasma CRP levels [86] rs3091244 High Plasma CRP levels [49] rs1800947 Arterial pulse-wave velocity [49] TNF-α -308G>A rs3091256 CAD [58,60,61,66,67] Obesity [63] Insulin resistance [64] Metabolic syndrome [62] Plasma CRP levels [65] CAD -Coronary Artery Disease, CIMT -Carotid Intima Media Thickness, CRP-C-reactive protein, IL 6 -Interleukin 6, MI-Myocardial Infarction, PAD -Peripheral Arterial Disease, SNP -Single Nucleotide Polymorphism, TNF-α -Tumor necrosis factor-alpha. Note: References given in brackets.…”