Location: Location not imported yet.Title: APOA2, dietary fat and body mass index: replication of a gene-diet interaction in three independent populations) Author
|Cupples, L adrienne|
|Lai, Chao qiang|
Submitted to: Archives of Internal Medicine
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/24/2009
Publication Date: 11/9/2009
Citation: Corella, D., Peloso, G., Arnett, D.K., Demissie, S., Cupples, L., Tucker, K., Lai, C., Parnell, L.D., Coltell, O., Lee, Y., Ordovas, J.M. 2009. APOA2, dietary fat and body mass index: replication of a gene-diet interaction in three independent populations. Archives of Internal Medicine. 169:1897-1906. Interpretive Summary: Nutrigenetics studies the role of genetic variation on interactions or interplay between diet and health aimed at providing personalized dietary advice. Many intriguing results, however, have often failed to replicate in other sets of individuals. Thus, our study sought to examine the interaction between a specific genetic variant of APOA2, which shows functional consequence, food intake and body mass index (BMI, a measure of obesity) and to seek replication. Three independent populations were studied, one with records allowing for 20-year follow-up analysis. We assayed the influence of dietary saturated fat on the effects of the gene variant in the APOA2 gene, APOA2-265T>C, with BMI and risk of obesity in 3462 persons (2532 Whites and 930 Hispanics of Caribbean origin. Across all three studies, there was a significant effect or interaction between persons carrying two copies of the less common version of the APOA2 variant and high intake of saturated fat on BMI. The average increase in BMI was 6.2%. No such differences in BMI were seen when consumption of saturated fat was low. Similar results were observed for risk of obesity. In conclusion, for the first time, the interplay between diet and gene variant determining BMI and obesity risk has been strongly and consistently replicated in three independent populations and this strengthens the inference of causality of this gene variant.
Technical Abstract: Background: Nutrigenetics studies the role of genetic variation on interactions between diet and health aimed at providing more personalized dietary advice. However, replication has been very low and our aim was to study the interaction between a functional polymorphism of the APOA2 gene, food intake and body mass index (BMI) in independent populations to replicate findings and to increase their evidence level. Methods: Cross-sectional, follow-up (20 years) and case-control analyses were undertaken in three independent populations. We analyzed gene-diet interactions between the APOA2-265T>C polymorphism and saturated fat (SATFAT) intake on BMI and obesity risk in 3,462 subjects from three American populations: Framingham (1,454 Whites), GOLDN (1,078 Whites) and Boston-Puerto Rican studies (930 Hispanics of Caribbean origin). Results: Prevalence of CC subjects ranged from 11-15%. We identified statistically significant interactions between the APOA2-265T>C and SATFAT on BMI in all three populations. Thus, a significant association between the CC genotype and higher BMI (mean increase of 6.2%, ranging from 4.3%-7.9%; P<0.05) was observed with high, but not with low, SATFAT intake in all studies. Likewise, the CC genotype was significantly associated with higher obesity risk in all three populations only in the high-SATFAT stratum. Meta-analysis estimations of obesity risk for CC compared with TT+TC subjects were: OR=1.84, 95%CI:1.38-2.47; P<0.0001 in the high-SATFAT stratum, but no association was detected in the low-SATFAT stratum (OR=0.81, 95%CI:0.59-1.11;P=0.181). Conclusions: For the first time, a gene-diet interaction determining BMI and obesity risk has been strongly and consistently replicated in three independent populations, enhancing the inference of causality.