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

• Published in: Gene 2019-02, Vol.685, p.211-221
• Main Authors: Gomes Torres, Ana Cláudia M.B., Leite, Neiva, Tureck, Luciane Viater, de Souza, Ricardo Lehtonen Rodrigues, Titski, Ana Cláudia Kapp, Milano-Gai, Gerusa Eisfeld, Lazarotto, Leilane, da Silva, Larissa Rosa, Furtado-Alle, Lupe
• Format: Article
• Language: English
• Subjects: Innate immune system; Metabolism; NLR; Polymorphisms; TLR
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2018.11.065

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. •A allele carriers (rs13105517, TLR2) had higher HDL levels in children and adolescents.•G allele (rs455060, NLRC4) was associated with insulin and TG levels in both samples.•C allele (rs212704, NLRC4) was associated with insulin and QUICKI index.•G allele carriers (rs7258674, CARD8) had higher glucose levels in both samples.•G allele (rs6671879, NEK7) was associated with higher LDL-C and TC levels.