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[白细胞介素-6和纤维蛋白原编码基因的多态性变体、缺血性中风风险及纤维蛋白原水平]

[Polymorphic variants of genes encoding interleukin-6 and fibrinogen, the risk of ischemic stroke and fibrinogen levels].

作者信息

Titov B V, Barsova R M, Martynov M Iu, Nikonova A A, Favorov A V, Gusev E I, Favorova O O

出版信息

Mol Biol (Mosk). 2012 Jan-Feb;46(1):93-102.

Abstract

Carriage frequencies of alleles and genotypes of polymorphous locus of -174G>C IL6 (rs1800795) were analyzed in the patients with ischemic stroke (IS) of Russian ethnic descent (200 cases) and in the control group of the same ethnic descent with similar sex and age (140 controls). Significant differences were identified in frequencies of carriage (in homo- or heterozygous form) of allele IL6*-174G (p = 0.0029, OR = 2.9, 95% CI: 1.4-5.8), which can be considered as risk factor for IS and in frequencies of IL6*-174C/C genotype carriage, correspondingly (p = 0.0029, OR = 0.35, 95% CI: 0.17-0.69). After sex stratification of patients and controls similar significant differences were observed only between female patients and controls, after age stratification the difference was observed only for the age group older 60 years. Complex analysis of association of SNP -174G>C IL6 alleles and genotypes carriage in combination with SNP 4266A>G (Thr312Ala) FGA (rs6050) (see symbol) -249C>T FGB (rs1800788) with IS revealed protective combinations IL6*-174C/C + FGA* 4266A (see symbol) IL6*-174C/C + FGB*-249C, which were slightly more significant than single protective genotype IL6*-174C/C associated with IS and their ORs didn't differ substantially from the single genotypes's OR value. At the same time the combinations of alternative allele IL6*-174G with the same FGB*-249C or FGA* 4266A alleles were revealed and their association significance levels as well as OR values were lower than the values for the single risk allele IL6*-174G. In case of the mutual carriage of IL6*-174G allele with FGA4266A/A, FGB-249C/C genotypes or with combinations of these alleles/genotypes the "neutralized" effect became stronger. In other words, we observed association of IS with allele/genotype combinations of genes IL6, FGA and FGB, in which IL6 plays key role and FGA and FGB have modulating function. In analysis of association of fibrinogen plasma levels with three analyzed polymorphous loci significant differences were not revealed.

摘要

对俄罗斯族裔缺血性中风(IS)患者(200例)和相同族裔、性别和年龄相似的对照组(140例),分析了-174G>C IL6(rs1800795)多态性位点的等位基因和基因型携带频率。发现等位基因IL6*-174G(纯合或杂合形式)的携带频率存在显著差异(p = 0.0029,OR = 2.9,95%CI:1.4 - 5.8),可将其视为IS的危险因素,相应地,IL6*-174C/C基因型的携带频率也存在显著差异(p = 0.0029,OR = 0.35,95%CI:0.17 - 0.69)。对患者和对照组进行性别分层后,仅在女性患者和对照组之间观察到类似的显著差异;进行年龄分层后,仅在60岁以上年龄组观察到差异。对SNP -174G>C IL6等位基因和基因型携带与SNP 4266A>G(Thr312Ala)FGA(rs6050)(见符号)-249C>T FGB(rs1800788)组合与IS的关联进行综合分析,发现了保护性组合IL6*-174C/C + FGA* 4266A(见符号)、IL6*-174C/C + FGB*-249C,它们比与IS相关的单一保护性基因型IL6*-174C/C略显著,且其OR值与单一基因型的OR值没有实质性差异。同时,发现了替代等位基因IL6*-174G与相同的FGB*-249C或FGA* 4266A等位基因的组合,其关联显著水平和OR值低于单一风险等位基因IL6*-174G的值。当IL6*-174G等位基因与FGA4266A/A、FGB-249C/C基因型或这些等位基因/基因型的组合相互携带时,“中和”效应更强。换句话说,我们观察到IS与IL6、FGA和FGB基因的等位基因/基因型组合有关联,其中IL6起关键作用,FGA和FGB具有调节功能。在分析纤维蛋白原血浆水平与三个分析的多态性位点的关联时,未发现显著差异。

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