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Background  Apolipoprotein A-V (ApoA-V) is a recognized regulator of plasma triglycerides (TGs), and previous studies have shown associations between variants in  APOA5  (apolipoprotein-A5) gene and high TG levels. Recently, a new association between the Arg282Ser missense mutation (rs778114184 G > T) in  APOA5  gene and decreased triglyceride levels has been shown in an adult population from Sardinia.  In this study we add further insight into the role of  APOA5  by exploring whether this association begins early in life in children, or becomes manifest only in adulthood. We performed the genetic association analysis of  APOA5  in a cohort of 925 overweight and obese children and adolescents from Sardinia, Italy, to see if the genetic burden is already at play before modifying risk factors are interacting.    Results  We identified 24 heterozygous subjects for the Arg282Ser variant and no homozygous subject. Here we show that the Arg282Ser mutation in  APOA5  gene is associated with a significant reduction of TG (−15.5 mg/dl), total (−18.1 mg/dl) and LDL-cholesterol (−14.8 mg/dl) levels in overweight/obese children and adolescents, indicating that indeed this association appears early in life. Also, we observed a significant reduction in serum apoA-V levels in heterozygous children.    Conclusions  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.

lipids in health and disease

The Arg282Ser missense mutation in APOA5 gene determines a reduction of triglyceride and LDL-cholesterol in children, together with low serum levels of apolipoprotein A-V