Association of interleukin-6 gene G-174C polymorphism and plasma plasminogen activator inhibitor-1 level in Chinese patients with and without hypertension

Jeng, Jing-Ren; Wang, Ji Hung; Liu, Wei Shin; Chen, Shee Ping; Chen, Michael Yu Chih; Wu, Meng Hsiu; Hsu, Wen Lin; Lin, Shinn Zong

doi:10.1016/j.amjhyper.2004.10.028

Cited by 16 publications

(12 citation statements)

References 29 publications

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“…The IL6 *C allele was associated with elevated blood pressure in dialysis patients (Losito et al 2003). Chinese hypertensive patients, in contrast with Caucasians, were found to have an increased number of -174*G/*G homozygotes compared with normotensive subjects (Jeng et al 2005). This finding suggests that ethnicity along with gender-dependent factors might influence the effect of genetic polymorphism on interleukin expression.…”

Section: Discussionmentioning

confidence: 95%

Association of Interleukin-6, Interleukin-12, and Interleukin-10 Gene Polymorphisms with Essential Hypertension in Tatars from Russia

Timasheva

Nasibullin²,

Zakirova

et al. 2007

Biochem Genet

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Essential hypertension is a common disease with fatal clinical complications. Epidemiological and family studies have confirmed the role of genetic predisposition in its development. Hypertensive patients have been shown to have an altered profile of pro- and anti-inflammatory cytokines. The aim of our investigation was to reveal the association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension and its clinical complications in a Tatar ethnic group from Bashkortostan, Russia. The study involved 362 hypertensive patients and 244 healthy subjects from this Tatar ethnic group (Bashkortostan, Russia). DNA was isolated from whole venous blood using phenol-chloroform extraction by the standard method. IL6 -572 G/C, IL12B 1159 C/A, and IL10 -627 C/A genotypes were typed using polymerase chain reaction followed by restriction enzyme digestion. We found that the IL10 -627 *C/*C genotype was associated with decreased risk of hypertension (OR = 0.64, P = 0.035). IL6 genotypes and allele distribution did not differ significantly between subjects with and without hypertension, but the IL6 -572 *G/*G genotype frequency was found to be significantly higher among those patients who had stroke, compared with normotensive control subjects (P = 0.036). Carriers of the IL12B 1159 *A/*A genotype had a lower risk of stroke (OR = 0.38, P = 0.028). Our study has shown the association between IL10 -627 C/A polymorphism and essential hypertension in the Tatar ethnic group from Bashkortostan, Russia. The IL10 -627*C/*C genotype was found to be protective against hypertension. We also demonstrated that hypertensive patients with the IL12B *A/*A and IL6 *G/*G genotypes had increased risk of stroke. Our results suggest a role for cytokines in cardiovascular disease development in the Tatar ethnic group, but further investigation is needed.

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Section: Discussionmentioning

confidence: 95%

Association of Interleukin-6, Interleukin-12, and Interleukin-10 Gene Polymorphisms with Essential Hypertension in Tatars from Russia

Timasheva

Nasibullin²,

Zakirova

et al. 2007

Biochem Genet

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“…Given the close association of adiponectin and PAI-1, it was not surprising to observe an impact of adiponectin T94G genotype on plasma PAI-1 levels. This genotype effect might be mediated indirectly through its influence on adiponectin production, or it could be in linkage disequilibrium with some functional/etiological variants on the adiponectin gene locus like the examples of PAI-1 4G/5G polymorphism [23 ]or IL-6-174 polymorphism [24], that may affect plasma PAI-1 levels. Obviously, it would not suffice to state for a direct, causal relationship between adiponectin genotype and plasma PAI-1 since this is only a cross-sectional survey in a particular population.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the possible association of this genotype with plasma PAI-1 had not been reported yet. Our previous studies [21,22,23,24]had shown correlations of elevated plasma PAI-1 to insulin resistance, dyslipidemia, hypertension, PAI-1 promoter 4G/4G and interleukine-6 (IL-6) –174GG genotype but not to angiotensin-I converting enzyme DD genotype. In this study, the adiponectin genotype and the plasma levels of adiponetcin and PAI-1 were determined in patients with and without hypertension to explore the interrelationships of G94T genotype, plasma adiponectin, PAI-1, and blood pressure.…”

Section: Introductionmentioning

confidence: 99%

Plasma Adiponectin, T94G Gene Polymorphism and PAI-1 in Patients with and without Hypertension

Jeng

2006

Cardiology

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Background: Reduced adiponectin level has been associated with metabolic syndrome, type 2 diabetes, coronary artery disease and gene polymorphisms, but the interrelationships of T94G genotype, plasma adiponectin and plasminogen activator inhibitor-1 (PAI-1) are less understood. Patients and Methods: The T94G genotypes and plasma levels of adiponectin, and PAI-1 were determined in 568 Chinese patients, 212 with and 356 without hypertension, to study the possible associations of T94G genotype, plasma adiponectin, PAI-1 and blood pressure. Results: Hypertensive patients showed significantly lower plasma adiponectin (9.7 ± 11.1 vs. 11.5 ± 10.0 µg/ml, p = 0.04) and higher PAI-1 (p < 0.001) levels but not significantly greater adiponectin TT genotype percentage (38.7 vs. 33.5%) and T allele frequency (0.620 vs. 0.585) than normotensive subjects. Plasma adiponectin was inversely related to PAI-1 activity (r = –0.09, p = 0.03) and antigen (r = –0.202, p < 0.001). Furthermore, the TT genotypic group showed significantly lower plasma adiponectin level (10.4 ± 10.5 vs. 13.4 ± 10.8 µg/ml, p = 0.03) and higher plasma PAI-1 activity (17.0 ± 9.7 vs. 13.5 ± 7.6 IU/ml, p = 0.003) and antigen (32.3 ± 22.7 vs. 25.9 ± 14.7 ng/ml, p = 0.01) than the GG genotypic group. Multiple linear regression analysis in all study subjects, in men and in normotensives documented an impact of adiponectin T94G genotype on plasma levels of adiponectin (p = 0.007, 0.003 and 0.03) and PAI-1 activity (p = 0.02, 0.03 and 0.04) and antigen (p = 0.03, 0.007 and 0.04) after adjustment for potential confounding factors. Conclusions: The present study demonstrated a significant correlation of the TT genotype with lower plasma adiponectin and higher plasma PAI-1 levels in a Chinese population. The contribution of this genotype seemed greater in men and normotensives. It suggested the adiponectin gene T94G polymorphism might affect the regulation of circulating adiponectin and PAI-1.

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“…19,29 Given the role of IL-6 as a key mediator of acute phase reaction, single nucleotide polymorphisms (SNPs) in the IL-6 gene (IL6) have gained much attention, and a number of SNPs in the IL-6 gene promoter have been found to be related to the concentrations of acute phase proteins. [30][31][32][33][34] The IL-6 gene À174G4C polymorphism has been associated with PAI-l level in patients with or without hypertension, 30 and À174GG genotype has been associated with lower IL-6 levels after coronary artery bypass grafting (CABG) 31 and lower baseline fibrinogen levels in those subjects with CRP 40.33 mg/l. 32 The IL6 À174C4T polymorphism has been found to explain 14% of the baseline plasma CRP level.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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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.

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Association of interleukin-6 gene G-174C polymorphism and plasma plasminogen activator inhibitor-1 level in Chinese patients with and without hypertension

Cited by 16 publications

References 29 publications

Association of Interleukin-6, Interleukin-12, and Interleukin-10 Gene Polymorphisms with Essential Hypertension in Tatars from Russia

Association of Interleukin-6, Interleukin-12, and Interleukin-10 Gene Polymorphisms with Essential Hypertension in Tatars from Russia

Plasma Adiponectin, T94G Gene Polymorphism and PAI-1 in Patients with and without Hypertension

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

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