Association between the APOA2 promoter polymorphism and body weight in Mediterranean and Asian populations: replication of a gene-saturated fat interaction

D Corella, E S Tai, J V Sorlí, S K Chew, O Coltell, M Sotos-Prieto, A García-Rios, R Estruch, J M Ordovas, D Corella, E S Tai, J V Sorlí, S K Chew, O Coltell, M Sotos-Prieto, A García-Rios, R Estruch, J M Ordovas

Abstract

Objective: The APOA2 gene has been associated with obesity and insulin resistance (IR) in animal and human studies with controversial results. We have reported an APOA2-saturated fat interaction determining body mass index (BMI) and obesity in American populations. This work aims to extend our findings to European and Asian populations.

Methods: Cross-sectional study in 4602 subjects from two independent populations: a high-cardiovascular risk Mediterranean population (n = 907 men and women; aged 67 ± 6 years) and a multiethnic Asian population (n = 2506 Chinese, n = 605 Malays and n = 494 Asian Indians; aged 39 ± 12 years) participating in a Singapore National Health Survey. Anthropometric, clinical, biochemical, lifestyle and dietary variables were determined. Homeostasis model assessment of insulin resistance was used in Asians. We analyzed gene-diet interactions between the APOA2 -265T>C polymorphism and saturated fat intake (<or ≥ 22 g per day) on anthropometric measures and IR.

Results: Frequency of CC (homozygous for the minor allele) subjects differed among populations (1-15%). We confirmed a recessive effect of the APOA2 polymorphism and replicated the APOA2-saturated fat interaction on body weight. In Mediterranean individuals, the CC genotype was associated with a 6.8% greater BMI in those consuming a high (P = 0.018), but not a low (P = 0.316) saturated fat diet. Likewise, the CC genotype was significantly associated with higher obesity prevalence in Chinese and Asian Indians only, with a high-saturated fat intake (P = 0.036). We also found a significant APOA2-saturated fat interaction in determining IR in Chinese and Asian Indians (P = 0.026).

Conclusion: The influence of the APOA2 -265T>C polymorphism on body-weight-related measures was modulated by saturated fat in Mediterranean and Asian populations.

Figures

Figure 1
Figure 1
Association between the APOA2 −265T>C polymorphism and body-weight in (A) Mediterranean subjects (n= 374 TT, 398 TC and 135 CC) and in (B) Asian Indians (n= 305 TT, 160 TC and 29 CC). Adjusted means and error bars by genotype. Means were adjusted for sex, age, tobacco smoking and alcohol consumption. * P values for mean comparison between CC and T allele carriers obtained in the multivariate adjusted models. Error bars: SE of means.
Figure 2
Figure 2
Interaction between the APOA2 −265T>C polymorphism and saturated fat intake on BMI in (A) Mediterranean subjects (n=772 T-allele carriers and n= 135CC) and in (B) Chinese and Asian Indians (n= 1483T-allele carriers and 28 CC sucjects). Adjusted means of BMI are shown depending on the APOA2 −265T>C polymorphism according to the strata of saturated fat intake (below and above 22g/d). Means were adjusted for sex, age (as continuous), tobacco smoking (as categorical), alcohol consumption (as categorical), diabetes status (as categorical), lipid medication (only in the Mediterranean population), ethnicity (in the Asian population) and total energy intake (as continuous). P values for the interaction terms between saturated fat intake (as dichotomous) and the APOA2 polymorphism in each population were obtained in the hierarchical multivariate interaction model. In the stratified analysis by saturated fat intake levels, P values for mean comparisons of BMI between APOA2 genotypes were estimated after multivariate adjustment for the covariates indicated above. Bars indicate standard error (SE) of means.
Figure 3
Figure 3
Interaction between the APOA2 −265T>C polymorphism and saturated fat intake in determining IR in Chinese (n=1204) and Asian Indians (n=307). Adjusted means of IR are shown depending on the APOA2 −265T>C polymorphism (n=1493 T-allele carriers and 28 CC) according to the strata of saturated fat intake (below and above 22g/d). Means were adjusted for sex, age (as continuous), ethnicity, tobacco smoking (as categorical), alcohol consumption (as categorical), and total energy intake (as continuous). P values for the interaction terms between saturated fat intake (as dichotomous) and the APOA2 polymorphism in each population were obtained in the hierarchical multivariate interaction model. In the stratified analysis by saturated fat intake levels, P values for mean comparisons of BMI between APOA2 genotypes were estimated after multivariate adjustment for the covariates indicated above. All statistical analyses were carried out with the ln transformed IR. Bars indicate standard error (SE) of means.

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