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

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.