APOA-5 Genetic Variant rs662799: Role in Lipid Changes and Insulin Resistance after a Mediterranean Diet in Caucasian Obese Subjects

Abstract

Background and Aims. This APOA5-1131C allele is related with a higher serum triglyceride levels and perhaps a different metabolic response to a dietary intervention. The aim of the present investigation was to evaluate SNP rs662799 in the APOA5 gene and its associations with metabolic effects after a hypocaloric diet with Mediterranean pattern. Methods. A population of 363 Caucasian obese patients was enrolled. Anthropometric parameters and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, adiponectin, resistin, and leptin levels) were measured, at basal time and after 3 months. All patients were genotyped in the rs662799 polymorphism. Results. The APOA5 variant distribution was as follows: 89.3% ( $n=324$ ) (TT) were homozygous for the T allele, 10.5% ( $n=38$ ) (TC) were heterozygous, and 0.2% ( $n=1$ ) (CC) were homozygous for the C allele. Triglyceride levels were higher in patients with the C allele. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, adiponectin, leptin, and adiponectin/leptin ratio improved significantly in both genotype groups TT and TC+CC. After dietary intervention, insulin levels (delta: $-3.6\pm 0.8\text{UI}/\text{L}$ vs. $-1.5\pm 0.6\text{UI}/\text{L}$ ; $P=0.03$ ), HOMA-IR (delta: $-1.5\pm 0.4\text{units}$ vs. $-0.3\pm 0.2\text{units}$ ; $P=0.02$ ), and triglyceride levels (delta: $-19.3\pm 4.2\text{mg}/\text{dL}$ vs. $-3.2\pm 3.1\text{mg}/\text{dL}$ ; $P=0.02$ ) decreased in non-C allele carriers. Conclusions. C allele carriers of rs662799 of the APOA5 gene did not show an improvement in triglyceride, insulin, and HOMA-IR levels after a significant weight loss due to a hypocaloric diet with a Mediterranean pattern.