Submitted to: Obesity
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/2/2009
Publication Date: 2/1/2010
Citation: Smith, C.E., Tucker, K.L., Parnell, L.D., Lai, C., Lee, Y., Ordovas, J.M. 2010. Apolipoprotein A5 and lipoprotein lipase interact to modulate anthropometric measures in Hispanics of Caribbean origin. Obesity. 18(2):327-332. Interpretive Summary: The breakdown of lipids, a type of fat, is in part coordinately regulated by APOA5 (apolipoprotein A5) and LPL (lipoprotein lipase) and genetic variants of these two genes have been associated independently with obesity risk. Evaluating gene combinations may be more effective than analyses of single genetic variants in identifying genetic risk, but low occurrence of the variants associated with elevated risk often limits evaluations of potential gene-to-gene relationships. Populations comprised of multiple ancestries provide unique opportunities to evaluate such gene-to-gene interactions. We examined relationships between variants of LPL and APOA5 and lipid and anthropometric measures in 1019 Caribbean-origin Hispanics. Significant interactions between the LPL and APOA5 variants with respect to measures of obesity (e.g., body mass index, waist and hip girth) were observed. Additionally, risk extreme obesity (BMI above 40) was correlated with the more rare variants of both LPL and APOA5. Thus, because these variants of the LPL and APOA5 genes are not so rare in this population of Caribbean-origin Hispanics, we were able to note that the less common versions of these genes interact in a genetic way to increase obesity risk.
Technical Abstract: Apolipoprotein A5 (APOA5) and lipoprotein lipase (LPL) proteins interact functionally to regulate lipid metabolism, and single nucleotide polymorphisms (SNPs) for each gene have also been associated independently with obesity risk. Evaluating gene combinations may be more effective than single SNP analyses in identifying genetic risk, but insufficient minor allele frequency (MAF) often limits evaluations of potential epistatic relationships. Populations with multiple ancestral admixtures may provide unique opportunities for evaluating genetic interactions. We examined relationships between LPL m107 (rs1800590) and APOA5 S19W (rs3135506) and lipid and anthropometric measures in Caribbean origin Hispanics (n=1019, aged 45-75 years) living in the Boston metropolitan area. Significant interaction terms between LPL m107 and APOA5 S19W were observed for BMI (P=0.003) and waist circumference (P=0.019). Higher BMI (P=0.001), waist (P=0.011) and hip (P=0.026) were observed in minor allele (G) carriers for LPL m107 who also carried the APOA5 S19W minor allele (G). Additionally, extreme obesity (BMI=40 kg/m2) risk was higher (OR=4.02; 95% CI:1.81-8.91; global P=0.008) for minor allele carriers for both SNPs (LPL TG+GG, APOA5 CG+GG) compared to major allele carriers for both SNPs. In summary, we identified significant interactions for APOA5 S19W and LPL m107 for obesity in Caribbean Hispanics. Population-specific MAFs increase the difficulties of replicating gene-gene interactions, but may support the hypothesis that combinations of frequencies in selected genes could heighten obesity susceptibility in a given population. Analyses of gene-gene interactions may improve understanding of genetically-based obesity risk, and underscore the need for further study of groups with multiple ancestral admixtures.