促炎细胞因子基因单核苷酸多态性在健康男性血脂与炎症参数关系中的作用以及鱼油的降脂效果

Role of single nucleotide polymorphisms of pro-inflammatory cytokine genes in the relationship between serum lipids and inflammatory parameters, and the lipid-lowering effect of fish oil in healthy males.

作者信息

Markovic Olivera, O'Reilly Gillian, Fussell Helen M, Turner Stephen J, Calder Philip C, Howell William M, Grimble Robert F

机构信息

Institute of Human Nutrition, School of Medicine, University of Southampton, S016 7PX, UK.

出版信息

Clin Nutr. 2004 Oct;23(5):1084-95. doi: 10.1016/j.clnu.2004.02.002.

DOI:10.1016/j.clnu.2004.02.002

PMID:15380900

Abstract

BACKGROUND AND AIMS

Lipid metabolism, obesity and inflammation are intimately related. Plasma triglycerides increase during the inflammatory response to pathogens and obesity increases inflammatory stress. Pro-inflammatory cytokines are secreted by adipocytes in uninfected obese subjects. Polymorphisms (SNPs) in cytokine genes influence the intensity of cytokine production and inflammatory stress. Fish oil has lipid-lowering and anti-inflammatory properties. The influence of cytokine gene polymorphisms on the interaction between adiposity, inflammation and the properties of fish oil is unknown.

METHODS

Fasting plasma triglycerides, acute phase proteins and BMI were studied in 159 healthy men and the effect of 6 g/d fish oil for 12 weeks on the former two parameters studied. Subjects were genotyped for SNPs at positions -511, -174, +252 and -308 in the IL-1beta, IL-6, LT-alpha (TNF-beta) and TNF-alpha genes, respectively. Data were divided into three sub-groups of BMI, 16.7-22.8, 22.9-24.9 and 25.1-33.7 kg/m2, respectively.

RESULTS

Correlations were apparent between CRP and triglycerides in the highest tertile r = 0.324, P < 0.05 and between CRP and serum amyloid in all tertiles. Mean concentrations of all three molecules were higher in the middle and highest tertile than in the lowest. Irrespective of BMI, CRP and triglycerides were positively correlated in subjects with a TNF-alpha-308GG, LT-alpha AG, IL-1beta-511TT and IL-6-174GG genotype. The latter three genotypes are associated with enhanced inflammation. Genotype and BMI interacted. Concentrations of triglyceride rose significantly with increasing tertile only in subjects with a LT-alpha AA genotype. CRP concentrations rose in subjects with a LT-alpha AG genotype. Triglycerides were lowered by fish oil. Pre-supplementation concentrations were correlated with the decrease, r = -0.494 P < 0.0001. Genotype influenced the effects of fish oil. A fall occurred in triglycerides, across tertiles of BMI, only in individuals possessing a LT-alpha+252 AA genotype. Irrespective of BMI, possession of an A allele of this SNP was necessary for the correlation to occur.

CONCLUSIONS

Possession of genotypes associated with raised inflammatory stress strengthen the association between fasting plasma triglycerides and CRP. The ability of fish oil to exert a lipid-lowering, anti-inflammatory influence in healthy men is influenced by BMI and possession of the LT-alpha+252 A allele.

摘要

背景与目的

脂质代谢、肥胖与炎症密切相关。在对病原体的炎症反应过程中血浆甘油三酯会升高，而肥胖会增加炎症应激。未感染的肥胖受试者体内的脂肪细胞会分泌促炎细胞因子。细胞因子基因中的多态性（单核苷酸多态性，SNPs）会影响细胞因子产生的强度以及炎症应激。鱼油具有降血脂和抗炎特性。细胞因子基因多态性对肥胖、炎症以及鱼油特性之间相互作用的影响尚不清楚。

方法

对159名健康男性的空腹血浆甘油三酯、急性期蛋白和体重指数进行了研究，并研究了每日6克鱼油连续服用12周对前两个参数的影响。分别对受试者的白细胞介素-1β（IL-1β）基因-511位、白细胞介素-6（IL-6）基因-174位、淋巴毒素-α（LT-α，肿瘤坏死因子-β）基因+252位和肿瘤坏死因子-α（TNF-α）基因-308位的单核苷酸多态性进行基因分型。数据被分为体重指数的三个亚组，分别为16.7 - 22.8、22.9 - 24.9和25.1 - 33.7kg/m²。

结果

在最高三分位数组中，C反应蛋白（CRP）与甘油三酯之间存在明显相关性（r = 0.324，P < 0.05），并且在所有三分位数组中CRP与血清淀粉样蛋白之间也存在相关性。所有这三种分子的平均浓度在中间和最高三分位数组中高于最低三分位数组。无论体重指数如何，在具有TNF-α - 308GG、LT-α AG、IL-1β - 511TT和IL-6 - 174GG基因型的受试者中，CRP与甘油三酯呈正相关。后三种基因型与炎症增强相关。基因型和体重指数存在相互作用。仅在具有LT-α AA基因型的受试者中，甘油三酯浓度随三分位数增加而显著升高。具有LT-α AG基因型的受试者中CRP浓度升高。鱼油可降低甘油三酯。补充前的浓度与降低幅度相关（r = -0.494，P < 0.0001）。基因型影响鱼油的作用。仅在具有LT-α +252 AA基因型的个体中，跨体重指数三分位数组甘油三酯出现下降。无论体重指数如何，该单核苷酸多态性的A等位基因的存在是产生这种相关性的必要条件。