In multivariate regression models, the c56C > G SNP, plasma apoCIII, plasma nonesterified fatty acids, hepatic APOA5 transcripts, sex and a weak association with obesity status explained 61% of the variance in apoAV plasma levels.
In conclusion, we have replicated previous gene-diet interactions between APOA5 -1131T > C SNP and fat intake for obesity traits and detected a novel interaction for TG-rich lipoprotein concentrations.
Our results suggest that dietary fat intake modifies the effect of APOA5 and LEPR polymorphisms on serum triglycerides, cholesterol levels and obesity in young subjects.
Population studies conducted in various countries have demonstrated an association between single nucleotide polymorphisms (SNPs) in ApoA5 and the increased risk to cardiovascular disease and metabolic syndrome (including diabetes and obesity).
We found that: (i) genotypes, including those of APOA5S19W, APOA5 -1131T > C, APOE, GCKR, TRIB1 and TBL2/MLXIPL, were significantly associated with severe HTG; (ii) odds ratios for these genetic variables were significant in both univariate and multivariate regression analyses, irrespective of the presence or absence of diabetes or obesity; (iii) a significant fraction-about one-quarter-of the explained variation in disease status was associated with these genotypes.
APOA5-1131C minor allele carriers had a lower obesity risk (OR, 0.61, 95%; CI, 0.39-0.98; P = 0.032) and overweight risk (OR, 0.63, 95%; CI, 0.41-0.96; P = 0.031) compared with TT subjects in the high fat intake group (>or=30% of energy ) but not when fat intake was low (OR, 1.16, 95%; CI, 0.77-1.74; P = 0.47 and OR = 1.15, 95%; CI, 0.77-1.71; P = 0.48) for obesity and overweight, respectively).
The contributions of APOA5-1131CC homozygotes to obesity risk in those who consume higher TEI were all significantly high regardless of percentage of energy intake from dietary macronutrients.
Our data clearly show that the Arg282Ser mutation in APOA5 gene determines a reduction of TG, total and LDL-cholesterol and apolipoprotein A-V levels in overweight/obese children and adolescents, demonstrating that this mutation has the power to affect lipid levels already since childhood.
In current study two SNPs rs662799 risk allele G (P = 0.03) and rs3135506 risk allele C (P = 0.05) of APOA5 were found to be associated with significant higher risk of triglyceride levels, irrespective of age, sex, obesity, diabetes, hypertension and smoking.
The results revealed that methylation levels within HDAC4 and RAX2 loci were positively associated with obesity, while the methylation levels of loci within APOA5 and CES1 loci were negatively correlated with obesity.
The results of the present study suggested that apoA5 may serve as a potential therapeutic target for the treatment of obesity and its related disorders.
In this review, we focus on the association of gene and protein of apoA5 with obesity and metabolic syndrome, and provide new insights into the physiological role of apoA5 in humans, giving a potential therapeutic target for obesity and associated disorders.