Overweight modulates APOE and APOA5 alleles on the risk of severe hypertriglyceridemia

BackgroundThis study aimed to investigate whether the body mass index (BMI) in combination with genetic variations in APOE and APOA5_‘T’ alleles modulates the risk of sHTG.MethodsThere were 255 moderate HTG (TG ≥ 2.26 and < 5.65 mmol/L) and 176 sHTG (TG ≥ 5.65 mmol/L) and 304 controls (TG < 2.26 mmol/L) were recruited. APOE epsilon alleles were genotyped using sequence-specific primers; the APOA5_‘T’ allele (c.553G>T, rs2075291) was identified using a restriction site polymorphism. Overweight/obesity was defined as BMI ≥ 25 kg/m2 and non-overweight as BMI < 25 kg/m2.ResultsMultivariate logistic regression analysis showed, in addition to APOA5_‘T’ allele, a significant interaction between BMI ≥ 25 kg/m2 and APOE4 carriers on the risk of sHTG. Subjects with diagnosis of diabetes, current smoking, hypertension, levels of non-high density lipoprotein, and BMI ≥ 25 kg/m2 were significant determinants of sHTG. The odds ratio (95% confidence intervals) of overweight/obese APOE4 carriers for sHTG was 13.56 (4.89–37.59) more than those of non-overweight non-APOE4 carriers, while the odds ratio for sHTG in overweight/obese patients with the APOA5_‘T’ allele was 15.83 (7.77–32.26) higher than those of non-overweight non-APOA5 carriers.ConclusionsOverweight/obesity may potentiate the genetic variants of the APOE4 and APOA5_‘T’ alleles on the risk of sHTG.

► Severe hypertriglyceridemia (sHTG) is a complex phenotype of gene and environment. ► Both APOE4 and APOA5_‘T’ allele are important genetic factors of sHTG. ► APOE4 or APOA5_‘T’ alleles acting synergistically with BMI to sHTG.