APOA5 Ala315>Val, identified in patients with severe hypertriglyceridemia, is a common mutation with no major effects on plasma lipid levels

Background: The importance of the APOA5 gene in determining plasma triglyceride (TG) levels has been demonstrated in transgenic and knockout mice and confirmed by human association studies in different ethnic groups. Methods: We screened for nonsynonomous APOA5 mutations in patients with plasma TG levels > 10 mmol/L. Coding sequence and promoter region of the APOA5 gene were sequenced in 95 individuals with severe hypertriglyceridemia (HTG). A large population sample of 3202 individuals was screened by PCR and restriction analysis for presence of detected mutation. Results: Three heterozygous carriers of 944C>T (Ala315>Val) were identified in the severe HTG patients, while twenty-two carriers were identified in the population sample. The rare allele frequency of the Val315 was significantly higher in HTG sample than in controls (0.016 vs 0.003, p<0.01, respectively). Most of the control Ala315Val carriers however had plasma lipid levels (triglycerides, total– and HDL– cholesterol) within the usual range detected in the population. Conclusions: APOA5 Ala315>Val does not play any dominant/important role in the genetic determination of plasma triglyceride levels but the increased frequency in HTG patients compared to controls suggest that it might interact with other gene variants to cause HTG.