title: The leptin receptor Gln223Arg polymorphism (rs1137101) mediates the postprandial lipaemic response, but only in males.
abstract: OBJECTIVE
  An exaggerated postprandial triacylglycerol (TAG) response is an important determinant of cardiovascular disease risk. With increased recognition of the role of leptin in systemic macronutrient metabolism, we used a candidate gene approach to examine the impact of the common leptin receptor (LEPR) Gln223Arg polymorphism (rs1137101) on postprandial lipaemia.
  
  
  RESULTS
  Healthy adults (n = 251) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (t = 0) and lunch (t = 330 min). Fasting total- and low-density lipoprotein cholesterol were 9% lower in the ArgArg than GlnArg group (P < 0.04), whereas fasting TAG was 27% lower in the ArgArg than GlnGln group (P < 0.02). The magnitude of the postprandial TAG response was also significantly lower in the ArgArg compared with the GlnArg and GlnGln genotypes, with a 26% lower area under the curve (AUC) and incremental AUC in the ArgArg individuals (P ≤ 0.023). Genotype*gender interactions were evident for fasting and postprandial TAG responses (P < 0.05), with the genotype effect only evident in males. Regression analysis indicated that the LEPR genotype and genotype*gender interactions were independent predictors of the TAG AUC, accounting for 6.3% of the variance. Our main findings were replicated in the independent LIPGENE-Cordoba postprandial cohort of metabolic syndrome subjects (n = 75), with a 52% lower TAG AUC in the ArgArg than GlnGln male subjects (P = 0.018).
  
  
  CONCLUSIONS
  We report for the first time that the common LEPR Gln223Arg genotype is an important predictor of postprandial TAG in males. The mechanistic basis of these associations remains to be determined.
authors.affiliation: Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences and Institute for Cardiovascular and Metabolic Research, PO Box 226, Whiteknights, University of Reading, Reading RG6 6AP, UK. k.g.jackson@reading.ac.uk
authors.forename: Kim G
authors.initials: KG
authors.lastname: Jackson
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.forename: Rosalynn
authors.initials: R
authors.lastname: Gill
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Christine M
authors.initials: CM
authors.lastname: Williams
authors.forename: Jose
authors.initials: J
authors.lastname: López-Miranda
authors.forename: Anne M
authors.initials: AM
authors.lastname: Minihane
mesh_terms: D000328:Adult; D000368:Aged; D005215:Fasting; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D054411:Receptors, Leptin / Q000235:genetics* / Q000502:physiology; D014280:Triglycerides / Q000097:blood*
chemical_list: D008055:Lipids; D054411:Receptors, Leptin; D014280:Triglycerides