Apolipoprotein A5 and Lipoprotein Lipase Interact to Modulate Anthropometric Measures in Hispanics of Caribbean Origin

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 = 1,019, 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) circumference 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 (odds ratio = 4.02; 95% confidence interval: 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.

The paradox of ApoA5 modulation of triglycerides: Evidence from clinical and basic research

“…Similar associations were also observed in children with obesity (148 obese children and 46 with normal body weight) were more than 68% of the obese children were positive for S19W ApoA5 allele along with G-75A allele in ApoA1 [55]. In obese individuals there was also a significant interaction between ApoA5 S19W and LDL m107 polymorphisms [56]. Four polymorphisms in ApoA5 (SNP1, SNP2, S19W and SNP3) has been correlated with high TG levels in diabetic women [57].…”

Apolipoprotein A5 deficiency aggravates high‐fat diet‐induced obesity due to impaired central regulation of food intake

“…In addition to dyslipidemia and in support of a role of APOA5 in the development of obesity, APOA5 gene variants have been associated with a greater degree of obesity in a number of epidemiological studies involving Caribbean Hispanics (23), pediatric patients (24), and Brazilian older adults (25). In part, this could be due to the proposed role of APOA5 in circulating lipid metabolism.…”

Central obesity in males affected by a dyslipidemia-associated genetic polymorphism on APOA1/C3/A4/A5 gene cluster

“…Two separate studies have found the association of WC with APOA5 rs3135506 in Hispanics, 42 and BMI with APOA5 rs2075291 in Chinese. 43 However, APOA5 rs3135506 genotype was found to be ubiquitous among our study group, while APOA5 rs2075291 was associated with increased TG but not BMI.…”