The -256T>C polymorphism in the apolipoprotein A-II gene promoter is associated with body mass index and food intake in the genetics of lipid lowering drugs and diet network study.
BACKGROUND
Apolipoprotein A-II (APOA2) plays an ambiguous role in lipid metabolism, obesity, and atherosclerosis.


METHODS
We studied the association between a functional APOA2 promoter polymorphism (-265T>C) and plasma lipids (fasting and postprandial), anthropometric variables, and food intake in 514 men and 564 women who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. We obtained fasting and postprandial (after consuming a high-fat meal) measures. We measured lipoprotein particle concentrations by proton nuclear magnetic resonance spectroscopy and estimated dietary intake by use of a validated questionnaire.


RESULTS
We observed recessive effects for this polymorphism that were homogeneous by sex. Individuals homozygous for the -265C allele had statistically higher body mass index (BMI) than did carriers of the T allele. Consistently, after multivariate adjustment, the odds ratio for obesity in CC individuals compared with T allele carriers was 1.70 (95% CI 1.02-2.80, P = 0.039). Interestingly, total energy intake in CC individuals was statistically higher [mean (SE) 9371 (497) vs 8456 (413) kJ/d, P = 0.005] than in T allele carriers. Likewise, total fat and protein intakes (expressed in grams per day) were statistically higher in CC individuals (P = 0.002 and P = 0.005, respectively). After adjustment for energy, percentage of carbohydrate intake was statistically lower in CC individuals. These associations remained statistically significant even after adjustment for BMI. We found no associations with fasting lipids and only some associations with HDL subfraction distribution in the postprandial state.


CONCLUSIONS
The -265T>C polymorphism is consistently associated with food consumption and obesity, suggesting a new role for APOA2 in regulating dietary intake.
Corella
Dolores
D
Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111-1524, USA.
Arnett
Donna K
DK
Tsai
Michael Y
MY
Kabagambe
Edmond K
EK
Peacock
James M
JM
Hixson
James E
JE
Straka
Robert J
RJ
Province
Michael
M
Lai
Chao-Qiang
CQ
Parnell
Laurence D
LD
Borecki
Ingrid
I
Ordovas
Jose M
JM
D016633:Apolipoprotein A-II / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight; D003627:Data Interpretation, Statistical; D004435:Eating; D005215:Fasting; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D011401:Promoter Regions, Genetic; D012737:Sex Factors
D016633:Apolipoprotein A-II; D008055:Lipids