Carbohydrate intake modifies associations between ANGPTL4[E40K] genotype and HDL-cholesterol concentrations in White men from the Atherosclerosis Risk in Communities (ARIC) study

Atherosclerosis. 2009 Mar;203(1):214-20. doi: 10.1016/j.atherosclerosis.2008.05.037. Epub 2008 Jul 2.


Background: Common allelic variation in the angiopoietin-like 4 gene (ANGPTL4[E40K]) has been associated with low triglyceride (TG) and high HDL-C.

Objective: We examined whether dietary macronutrient intake modified associations between ANGPTL4[E40K] variation and TG and HDL-C in White men and women from the Atherosclerosis Risk in Communities study.

Design: Diet was assessed by food frequency questionnaire. Intake of fat (total fat [TF], saturated fat [SF], monounsaturated fat [MUFA], polyunsaturated fat [PUFA], and n-3 PUFA) and carbohydrate were expressed as percentage of total energy intake. ANGPTL4 A allele carriers (n=148 in men, 200 in women) were compared to non-carriers (n=3667 in men, 4496 in women). Interactions were tested separately in men and women, adjusting for study center, age, smoking, physical activity, BMI, and alcohol intake.

Results: ANGPTL4 A allele carriers had significantly greater HDL-C and lower TG than non-carriers (p<or=0.001). In all participants, carbohydrate intake was inversely associated with HDL-C and positively associated with TG, whereas TF, SF, and MUFA showed opposite associations with TG and HDL-C (p<0.001). These relations were uniform between sex-specific genotype groups, with one exception. In men, but not women, the inverse association between carbohydrate and HDL-C was stronger in A allele carriers (beta+/-S.E. -1.80+/-0.54) than non-carriers (beta+/-S.E. -0.54+/-0.11, p(interaction)=0.04 in men and 0.69 in women; p 3-way interaction=0.14).

Conclusions: These data suggest that ANGPTL4 variation and relative contributions of dietary fat and carbohydrate influence TG and HDL-C concentrations. In men, ANGPTL4 variation and dietary carbohydrate may interactively influence HDL-C.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Angiopoietin-like 4 Protein
  • Angiopoietins / genetics*
  • Atherosclerosis / ethnology*
  • Atherosclerosis / genetics*
  • Cholesterol / metabolism*
  • Cholesterol, HDL / blood*
  • Community Health Services
  • Diet
  • European Continental Ancestry Group
  • Female
  • Genetic Variation
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Nutritional Sciences
  • Risk
  • Sex Factors
  • Triglycerides / blood*


  • ANGPTL4 protein, human
  • Angiopoietin-like 4 Protein
  • Angiopoietins
  • Cholesterol, HDL
  • Triglycerides
  • Cholesterol