The polymorphisms G(−174)C in IL6 gene and G(−1082)A in IL10 gene are associated with poor outcomes in patients with acute coronary syndrome

Blagodatskikh, Konstantin A.; Evdokimova, M. A.; Agapkina, Yu. V.; Nikitin, Alexey G.; Brovkin, A. N.; Pushkov, Alexander; Blagodatskikh, E. G.; Kudryashova, O. Yu.; Osmolovskaya, V. S.; Lo, Minushkina; Kochkina, M. S.; Selezneva, N.; Dankovtseva, E. N.; Чумакова, О. С.; Baklanova, T. N.; Talyzin, P. A.; Reznichenko, N. E.; Donetskaya, O. P.; Tereshchenko, S. N.; Красильникова, Е. С.; Джаиани, Н. А.; Акатова, Е В; Глезер, М. Г.; Galyavich, A. S.; Zakirova, V. B.; Козиолова, Н. А.; Timofeeva, Inessa; Yagoda, Alexandr; Игоревна, Боева Ольга; Katelnitskaya, L. I.; Khorolets, E. V.; Шлык, С В; Volkova, E. G.; Margaryan, M. P.; Guz, I. O.; Константинов, В. О.; Timofeeva, N. V.; Sidorenko, B A; Затейщиков, Д. А.; Носиков, В. В.

doi:10.1134/s0026893310050092

Cited by 4 publications

(5 citation statements)

References 33 publications

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“…Associations of certain alleles and geno types were not observed either with the predisposition to cardiac infarction or with an unfavorable outcome upon ACS. At the same time, the frequencies of geno types of the -174G>C polymorphic region obtained in the present work for the control subjects corre sponded to the frequencies of genotypes in patients with ACS [32], in patients with cardiac infarction, and in the control subjects (our unpublished data for the sampling investigated in [31]). At the same time, in both cases [31,32], combinations of alleles and geno types of IL6 and other inflammation genes were revealed which are associated with the disease.…”

Section: Resultsmentioning

confidence: 55%

“…At the same time, the frequencies of geno types of the -174G>C polymorphic region obtained in the present work for the control subjects corre sponded to the frequencies of genotypes in patients with ACS [32], in patients with cardiac infarction, and in the control subjects (our unpublished data for the sampling investigated in [31]). At the same time, in both cases [31,32], combinations of alleles and geno types of IL6 and other inflammation genes were revealed which are associated with the disease. We dis covered a protective effect of carriage of the IL6*-174C allele in combination with CCR5*d (rs333) and LTA*252G (rs909253) in the development of cardiac inf arction [31]; the association of an unfavorable outcome with combined carriage of the -174G/G genotype of IL6 and 1082G/A and 1082A/A genotypes of IL10 was revealed in patients with ACS [32].…”

Section: Resultsmentioning

confidence: 55%

“…At the same time, in both cases [31,32], combinations of alleles and geno types of IL6 and other inflammation genes were revealed which are associated with the disease. We dis covered a protective effect of carriage of the IL6*-174C allele in combination with CCR5*d (rs333) and LTA*252G (rs909253) in the development of cardiac inf arction [31]; the association of an unfavorable outcome with combined carriage of the -174G/G genotype of IL6 and 1082G/A and 1082A/A genotypes of IL10 was revealed in patients with ACS [32]. Comparison of these data with our results indicates a unidirectional influence of the polymorphic variants of SNP-174G>C of IL6 on the development of cardiovascular diseases: G is the risk allele and C is the protective allele exhibited more clearly in IS than in ischemic heart disease.…”

Section: Resultsmentioning

confidence: 94%

“…The association of -174G>C polymorphism of IL6 with the development of cardiovascular diseases in ethnic Russians was analyzed earlier upon cardiac inf arction [31] and acute coronary syndrome (ACS) [32], but not IS. Associations of certain alleles and geno types were not observed either with the predisposition to cardiac infarction or with an unfavorable outcome upon ACS.…”

Section: Resultsmentioning

confidence: 99%

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Polymorphic variants of the genes encoding intrleukin-6 and fibrinogen: Risk for ischemic stroke and fibrinogen levels

et al. 2012

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The occurrence of alleles and genotypes of polymorphic region -174G>C of the gene IL6 (rs1800795) in patients of Russian ethnicity with ischemic stroke (200 cases) and in the control of the same ethnicity similar in sex and age (140 control subjects) has been analyzed. Reliable differences were revealed in the carriage frequency of allele IL6*-174G in homozygous and heterozygous form (p = 0.0029, OR = 2.9, 95% CI: 1.4-5.8), which can be considered a risk factor for the development of ischemic stroke, and in the carriage frequencies of protective genotype IL6*-174C/C (p = 0.0029, OR = 0.35, 95% CI: 0.17-0.69), respectively. After the patients and the control subjects were divided by gender character, similar differences were observed only between women with ischemic stroke and those from the control group, and after division by age, they were only revealed in groups with members older than 60 years. Complex analysis of the associ ation of ischemic stroke with the carriage of alleles and genotypes of IL6 SNP-174G>C in combination with SNP 4266A>G (Thr312Ala) of the gene FGA (rs6050) and -249C>T of the gene FGB (rs1800788) revealed protective combinations of IL6*-174C/C + FGA*4266A and IL6*-174C/C + FGB*-249C, which are slightly more reliably associated with ischemic stroke than the one protective genotype IL6* -174C/C and have nearly the same OR value . At the same time, combinations of alternative allele IL6*-174G and the same alleles FGA*4266A or FGB*-249C were revealed that are characterized by a decrease in both the significance level and the OR value as compared with the carriage of one risk allele IL6*-174G. When there is a combined carriage of the allele IL6*-174G with the genotypes FGA*4266A/A, FGB*-249C/C or with combinations of these alleles/genotypes, the neutralizing effect is enhanced. In other words, we observed the association of IL6, FGA and FGB allele combinations with ischemic stroke in which IL6 plays the key role and FGA and FGB have a modulating function. In analyzing the association of the alleles/genotypes of three polymorphic regions with the fibrinogen level in plasma, no reliable difference was revealed.

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Section: Resultsmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

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Polymorphic variants of the genes encoding intrleukin-6 and fibrinogen: Risk for ischemic stroke and fibrinogen levels

et al. 2012

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“…19 Most population-based studies have observed that variants in the genes encoding interleukin-1 receptor antagonist, IL-6, IL-10, IL-16, IL-17A, and IL-18 are also genetically associated with atherosclerosis and CAD. [20][21][22][23][24] Recently, it was confirmed that the novel cytokine IL-33, a member of the IL-1 family, and its receptor ST2L-IL-1RL1 play important roles in inflammatory diseases. Furthermore, Miller et al demonstrated that the IL-33-ST2L pathway might inhibit the development of atherosclerosis.…”

Section: Introductionmentioning

confidence: 97%

The IL-33-ST2L Pathway Is Associated with Coronary Artery Disease in a Chinese Han Population

Nie

Liao

et al. 2013

The American Journal of Human Genetics

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The effects of interleukin-33 (IL-33) on the immune system have been clearly demonstrated; however, in cardiovascular diseases, especially in coronary artery disease (CAD), these effects have not yet been clarified. In this study, we investigate the genetic role of the IL-33-ST2L pathway in CAD. We performed three-stage case-control association analyses on a total of 4,521 individuals with CAD and 4,809 controls via tag SNPs in the genes encoding IL-33 and ST2L-IL-1RL1. One tag SNP in each gene was significantly associated with CAD (rs7025417(T) in IL33, padj = 1.19 × 10(-28), OR = 1.39, 95% CI: 1.31-1.47; rs11685424(G) in IL1RL1, padj = 6.93 × 10(-30), OR = 1.40, 95% CI: 1.32-1.48). Combining significant variants in two genes, the risk for CAD increased nearly 5-fold (padj = 8.90 × 10(-21), OR = 4.98, 95% CI: 3.56-6.97). Traditional risk factors for CAD were adjusted for the association studies by SPSS with logistic regression analysis. With the two variants above, both located within the gene promoter regions, reporter gene analysis indicated that the rs7025417 C>T and rs11685424 A>G changes resulted in altered regulation of IL33 and IL1RL1 gene expression, respectively (p < 0.005). Further studies revealed that the rs7025417 genotype was significantly associated with plasma IL-33 levels in the detectable subjects (n = 227, R(2) = 0.276, p = 1.77 × 10(-17)): the level of IL-33 protein increased with the number of rs7025417 risk (T) alleles. Based on genetic evidence in humans, the IL-33-ST2L pathway appears to have a causal role in the development of CAD, highlighting this pathway as a valuable target for the prevention and treatment of CAD.

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Genetic association analysis between IL9 and coronary artery disease in a Chinese Han population

et al. 2022

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The polymorphisms G(−174)C in IL6 gene and G(−1082)A in IL10 gene are associated with poor outcomes in patients with acute coronary syndrome

Cited by 4 publications

References 33 publications

Polymorphic variants of the genes encoding intrleukin-6 and fibrinogen: Risk for ischemic stroke and fibrinogen levels

Polymorphic variants of the genes encoding intrleukin-6 and fibrinogen: Risk for ischemic stroke and fibrinogen levels

The IL-33-ST2L Pathway Is Associated with Coronary Artery Disease in a Chinese Han Population

Genetic association analysis between IL9 and coronary artery disease in a Chinese Han population

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