title: Association of the tumor necrosis factor-alpha promoter polymorphism with change in triacylglycerol response to sequential meals.
abstract: 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 .
authors.affiliation: 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.
authors.forename: Kim G
authors.initials: KG
authors.lastname: Jackson
authors.affiliation: 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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: UCD Institute of Food & Health, University College Dublin, Dublin, Ireland.
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Ryan
authors.affiliation: UCD Institute of Food & Health, University College Dublin, Dublin, Ireland.
authors.forename: Eileen R
authors.initials: ER
authors.lastname: Gibney
authors.affiliation: UCD Institute of Food & Health, University College Dublin, Dublin, Ireland.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Brennan
authors.affiliation: UCD Institute of Food & Health, University College Dublin, Dublin, Ireland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.affiliation: Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Williams
authors.affiliation: 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.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.affiliation: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, UK. v.karani@reading.ac.uk.|Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK. v.karani@reading.ac.uk.
authors.forename: Karani S
authors.initials: KS
authors.lastname: Vimaleswaran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D062407:Meals; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D050177:Overweight / Q000097:blood; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D011401:Promoter Regions, Genetic; D016032:Randomized Controlled Trials as Topic; D014280:Triglycerides / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D006113:United Kingdom; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol
keywords: BMI; MECHE; Postprandial lipaemia; TNFA promoter polymorphism; Triacylglycerol