Population prevalence of APOE, APOC3 and PPAR-α mutations associated to hypertriglyceridemia in French Canadians

Abstract

Hypertriglyceridemia (HTG) is known as a common metabolic disorder associated with increased production, decrease catabolism and/or decreased hepatic uptake of triglyceride (TG)-rich particles. We assessed, in the Que´bec City population, the allele frequency and haplotype distributions of mutations in genes related to HTG, such as the apolipoprotein E (APOE) (C112R and C158R), the apolipoprotein CIII (APOC3) (C-482T and C3238G) and the peroxisome proliferator-activated receptor alpha (PPARa) (L162V) genes. A total of 938 anonymous unlinked newborns from the metropolitan Que´bec City area have been genotyped. Allele frequencies observed in the Que´bec City population differed from known frequencies determined in other Caucasian populations. The cotransmitted allele distribution between the two-marker genotypes APOE/APOC3(C3238G) and APOC3(C-482T)/PPARa(L162V) presented a weak deviation from the assumption of genetic independence. Also, we observed a non-independent distribution of the T-482/G3238 allele combinations within the APOC3 gene, suggesting strong linkage disequilibrium between the C-482T and C3238G polymorphisms. Moreover, comparisons of allele frequencies observed in the population of Que´bec City to those obtained in other Caucasian populations suggested that the population of Que´bec City may be at a lower risk of developing HTG due to APOE, APOC3 and PPARa genetic variants. However, the strong linkage disequilibrium and the two-marker genotype distributions observed in the APOC3 gene suggest that these two variants may functionally interact in the Que´bec City population.

The combination of ApoCIII, hepatic lipase and hormono sensitive lipase gene polymorphisms suggests an association with susceptibility to gestational hypertension

“…ApoCIII is a non-competitive LPL inhibitor, and ApoCIII gene polymorphisms can prevent an insulin effect on ApoCIII gene promoter, resulting in inappropriate LPL inhibition and increased plasma TG levels (Talmud and Humphries 1997). In the control group, the -482C > T and 3238C > G allele frequencies were similar to what was recently reported in French Canadians, with the -482C > T frequency being lower than in many other Caucasian populations (Garenc et al 2004). Interestingly, we found more cases of GH carrying the dyslipidemia-associated allele at both loci (-482T allele carriers, OR = 1.7; 3238G allele carriers, OR = 1.6), suggesting that women homozygous for both frequent ''protecting'' -482CC/ 3238CC ApoCIII genotypes were less susceptible to GH.…”

“…It is also noteworthy that the ApoCIII -482C > T and 3238C > G polymorphisms were in strong linkage disequilibrium (D' = 0.89; P < 0.0001), as was recently observed in French Canadians (D' = 0.80; P < 0.0001) (Garenc et al 2004). In the present study, the frequency of ApoCIII -482C > T and 3238C > G double heterozygotes was about 2.5-fold higher than expected (15.5% vs. 6.7%; Table 3).…”

PPARα-L162V polymorphism is not associated with schizophrenia risk in a Croatian population

“…Genotyping was performed in the Laboratory for Molecular Genetics (Department of Biology and Medical Genetics, School of Medicine, Rijeka) by polymerase chain reaction/restriction fragment length polymorphism analysis using protocol previously described [24].…”

Effect of the APOC3 Sst I SNP on fasting triglyceride levels in men heterozygous for the LPL P207L deficiency

“…Interestingly, the frequency of the S2 genotype seems to be more prevalent in LPL P207L-deficient patients from the present study than in a random population representing the metropolitan Québec City area. 23 However, it is not obvious to consider that patients bearing the LPL P207L mutation as well as the APOC3 S2 allele are those exhibiting a high lipid profile alteration that conduct them to the lipid clinic and this should be one raison that may explain the high APOC3 S2 allele frequency observed in LPL P20L patients. In the present study, the most intriguing results were observed with VLDL particles.…”