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Toll 样受体 (TLR) 和 NOD 样受体 (NLR) 多态性与脂质和糖代谢的关系。

Association between Toll-like receptors (TLR) and NOD-like receptor (NLR) polymorphisms and lipid and glucose metabolism.

机构信息

Department of Genetics, Federal University of Paraná, Francisco H. dos Santos, 210 Jardim das Américas, 81531-970 Curitiba, Paraná, Brazil.

Department of Physical Education, Federal University of Paraná, Coração de Maria, 92 Jardim Botânico, 80215-370 Curitiba, Paraná, Brazil.

出版信息

Gene. 2019 Feb 15;685:211-221. doi: 10.1016/j.gene.2018.11.065. Epub 2018 Nov 24.

Abstract

Recent evidences had shown activation of TLR (toll-like receptors) and NLR (nod-like receptors) in response to imbalance in nutrients intake, such as lipid and glucose. The main aim of this study was to investigate possible associations between 11 SNPs in TLR2, TLR4, NLRC4, CARD8 and NEK7 genes and lipid and glucose metabolism. Sample was composed by healthy children and adolescents (n = 158) and adults (n = 115). DNA extraction was obtained by salting-out and sample genotyping by matrix-assisted laser desorption ionization time-of-flight mass spectrometry based system. LDL-cholesterol, HDL-cholesterol, triglycerides, total cholesterol, glucose and insulin were measured by standard automated methods. Means were compared by t-test or Mann-Whitney test. Univariate and multivariate logistic regression were used to verify association between polymorphisms and lipid and glucose markers. Seven polymorphisms in 5 genes were associated with lipid and glucose parameters. For lipid parameters, the following associations were found: higher LDL-C levels and C allele of rs1554973 (TLR4) and G allele of rs6671879 (NEK7); higher HDL-cholesterol levels and A allele of rs13105517 (TLR2); higher total cholesterol and TT genotype of rs3804099 (TLR2) and G allele of rs6671879 (NEK7); higher triglycerides levels and G allele of rs455060 (NLRC4). For glucose parameters associations were found between C allele of rs7258674 (CARD8) and higher glucose levels, and between C allele of rs212704 (NLRC4) and G allele of rs455060 (NLRC4) and insulin levels. These findings indicate a relationship between polymorphisms of TLRs and NLRs genes and markers of lipid and glucose metabolism.

摘要

最近的证据表明,TLR( toll-like receptors )和 NLR( nod-like receptors )在营养摄入失衡时会被激活,例如脂质和葡萄糖。本研究的主要目的是研究 TLR2、TLR4、NLRC4、CARD8 和 NEK7 基因中的 11 个 SNP 与脂质和葡萄糖代谢之间可能存在的关联。样本由健康的儿童和青少年(n=158)和成年人(n=115)组成。通过盐析法提取 DNA,基质辅助激光解吸电离飞行时间质谱法对样本进行基因分型。采用标准自动化方法测定 LDL-胆固醇、HDL-胆固醇、甘油三酯、总胆固醇、葡萄糖和胰岛素。采用 t 检验或曼-惠特尼检验比较均值。采用单变量和多变量逻辑回归验证多态性与脂质和葡萄糖标志物之间的关联。5 个基因中的 7 个多态性与脂质和葡萄糖参数相关。对于脂质参数,发现以下关联:TLR4 的 rs1554973 中的 C 等位基因和 rs6671879(NEK7)中的 C 等位基因与 LDL-C 水平升高有关;TLR2 的 rs13105517 中的 A 等位基因与 HDL-胆固醇水平升高有关;TLR2 的 rs3804099 的 TT 基因型和 rs6671879(NEK7)中的 G 等位基因与总胆固醇水平升高有关;NLRC4 的 rs455060 的 G 等位基因与甘油三酯水平升高有关。对于葡萄糖参数,发现 CARD8 的 rs7258674 的 C 等位基因与较高的血糖水平之间存在关联,NLRC4 的 rs212704 与 rs455060(NLRC4)的 G 等位基因和胰岛素水平之间存在关联。这些发现表明 TLRs 和 NLRs 基因多态性与脂质和葡萄糖代谢标志物之间存在关系。

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