In Eastern Quebec, two major lipoprotein lipase (LPL) gene mutations, P207L and G188E, lead to complete LPL deficiency in homozygote subjects and contribute to elevated predisposition to hypertriglyceridemia in heterozygotes. First, we determined the allele frequencies of LPL (D9N, G188E, P207L, D250N, N291S, and S447X), APOE (C112R and C158R). PPAR alpha (L162V), and PPAR gamma 2 (P12A)single nucleotide polymorphisms (SNPs) in a random-based cohort of the metropolitan Quebec city area. Second, we compared the LPL X447 allele frequencies observed in the random cohort and in a cohort of LPL P207L deficient patients. In the random cohort, the LPL N9 rare allele exhibited a higher prevalence than previously expected (p = 0.0001). The LPL X447 allele frequency was lower in the patient cohort (Freq: 4.4%) than in the random cohort (Freq: 11.2%) (p = 0.0001). These results reveal the importance of genetic screening for LPL gene mutations D9N and S447X in a population at risk to develop hypertriglyceridemia. (c) 2006 Elsevier Inc. All rights reserved.