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

Association between Toll-like receptors (TLR) and NOD-like receptor (NLR) polymorphisms and lipid and glucose metabolism
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DOI:
10.1016/j.gene.2018.11.065
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发表时间:
2019-02-15
期刊:
影响因子:
3.5
通讯作者:
Furtado-Alle, Lupe
Furtado-Alle, Lupe
中科院分区:
生物学3区
文献类型:
--
作者:
Gomes Torres, Ana Claudia M. B.;Leite, Neiva;Furtado-Alle, Lupe

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最近的证据表明,在脂肪和葡萄糖等营养摄入失衡时,TLR(Toll样受体)和NLR(Nod样受体)会被激活。本研究的主要目的是探讨TLR2、TLR4、NLRC4、CADS和NEK7基因的11个SNPs与糖脂代谢的关系。样本由健康儿童青少年组(n=158)和成人组(n=115)组成。DNA提取采用盐析法,样品分型采用基质辅助激光解吸电离飞行时间质谱仪。用标准自动化方法测定低密度脂蛋白、高密度脂蛋白、甘油三酯、总胆固醇、血糖和胰岛素。均数比较采用t检验或Mann-Whitney检验。采用单因素和多因素Logistic回归分析,验证基因多态与血脂、血糖指标的相关性。5个基因中的7个多态性与血脂和血糖参数相关。在血脂指标方面,发现以下相关因素:rs1554973(TLR4)和rs6671879(NEK7)的低密度脂蛋白水平和C等位基因较高,rs13105517(TLR2)的高密度脂蛋白水平和A等位基因,rs3804099(TLR2)和rs6671879(NEK7)的总胆固醇和TT基因较高,rs455060(NLRC4)的甘油三酯水平和G等位基因较高。在血糖参数方面,rs7258674(CADS)的C等位基因与较高的血糖水平相关,rs212704(NLRC4)的C等位基因和rs455060(NLRC4)的G等位基因与胰岛素水平相关。提示TLRs和NLRs基因多态性与脂、糖代谢指标之间存在一定的相关性。
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, CARDS 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 (CARDS) 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.