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


METHODS
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.
Nettleton
Jennifer A
JA
Division of Epidemiology and Disease Control, University of Texas Health Science Center, Houston 1200 Herman Pressler Dr., Houston, TX 77030, United States. Jennifer.A.Nettleton@uth.tmc.edu
Volcik
Kelly A
KA
Hoogeveen
Ron C
RC
Boerwinkle
Eric
E
D000483:Alleles; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics*; D050197:Atherosclerosis / Q000208:ethnology* / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D003153:Community Health Services; D004032:Diet; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052756:Nutritional Sciences; D012306:Risk; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood*; D044465:White People
C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D008076:Cholesterol, HDL; D014280:Triglycerides; D002784:Cholesterol