Jackson Kim G, Li Yue, Ryan Miriam F, Gibney Eileen R, Brennan Lorraine, Roche Helen M, Williams Christine M, Lovegrove Julie A, Vimaleswaran Karani S
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, UK.
Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK.
Nutr J. 2016 Jul 25;15(1):70. doi: 10.1186/s12937-016-0190-9.
Reported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant's body weight. Hence, we investigated the association of TNFA polymorphism (-308G → A) with body mass index (BMI) and postprandial lipaemia and also determined the impact of BMI on the association of the polymorphism with postprandial lipaemia.
The study participants (n = 230) underwent a sequential meal postprandial study. Blood samples were taken at regular intervals after a test breakfast (t = 0, 49 g fat) and lunch (t =330 min, 29 g fat) to measure fasting and postprandial lipids, glucose and insulin. The Metabolic Challenge Study (MECHE) comprising 67 Irish participants who underwent a 54 g fat oral lipid tolerance test was used as a replication cohort. The impact of genotype on postprandial responses was determined using general linear model with adjustment for potential confounders.
The -308G → A polymorphism showed a significant association with BMI (P = 0.03) and fasting glucose (P = 0.006), where the polymorphism explained 13 % of the variation in the fasting glucose. A 30 % higher incremental area under the curve (IAUC) was observed for the postprandial TAG response in the GG homozygotes than A-allele carriers (P = 0.004) and the genotype explained 19 % of the variation in the IAUC. There was a non-significant trend in the impact of BMI on the association of the genotype with TAG IAUC (P = 0.09). These results were not statistically significant in the MECHE cohort, which could be due to the differences in the sample size, meal composition, baseline lipid profile, allelic diversity and postprandial characterisation of participants across the two cohorts.
Our findings suggest that TNFA -308G → A polymorphism may be an important candidate for BMI, fasting glucose and postprandial TAG response. Further studies are required to investigate the mechanistic effects of the polymorphism on glucose and TAG metabolism, and determine whether BMI is an important variable which should be considered in the design of future studies.
NCT01172951 .
肿瘤坏死因子-α（TNFA）与餐后甘油三酯（TAG）反应之间的报道关联并不一致，这可能是由于TNFA基因、膳食脂肪组成或参与者体重的差异所致。因此，我们研究了TNFA基因多态性（-308G→A）与体重指数（BMI）和餐后血脂异常的关联，并确定了BMI对该多态性与餐后血脂异常关联的影响。
研究参与者（n = 230）进行了连续餐食的餐后研究。在食用测试早餐（含49 g脂肪，t = 0）和午餐（含29 g脂肪，t = 330分钟）后定期采集血样，以测量空腹和餐后血脂、血糖及胰岛素水平。代谢挑战研究（MECHE）纳入了67名爱尔兰参与者，他们接受了54 g脂肪的口服脂质耐量试验，作为重复队列。使用一般线性模型并对潜在混杂因素进行调整，以确定基因型对餐后反应的影响。
-308G→A多态性与BMI（P = 0.03）和空腹血糖（P = 0.006）显著相关，该多态性解释了空腹血糖13%的变异。GG纯合子餐后TAG反应的曲线下增量面积（IAUC）比A等位基因携带者高30%（P = 0.004），且该基因型解释了IAUC中19%的变异。BMI对基因型与TAG IAUC关联的影响存在不显著的趋势（P = 0.09）。这些结果在MECHE队列中无统计学意义，这可能是由于两个队列在样本量、膳食组成、基线血脂谱、等位基因多样性和参与者餐后特征方面存在差异。
我们的研究结果表明，TNFA -308G→A多态性可能是BMI、空腹血糖和餐后TAG反应的重要候选因素。需要进一步研究来探讨该多态性对葡萄糖和TAG代谢的机制性影响，并确定BMI是否是未来研究设计中应考虑的重要变量。
NCT01172951 。
