Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy caucasian population

Background: Apolipoprotein A5 (APOA5) plays an important role in plasma triacylglycerol (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, and c.1259T>C) in the APOA5 gene define three common haplotypes (APOA5*1, APOA5*2, and APOA5*3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males. Design and Methods: Eighty-eight APO E3/3 volunteers [67 with (−1131T and 56C) APOA5*1 haplotype, 12 with (−1131C and 56C) APOA5*2 haplotype, and nine with (−1131T and 56G) APOA5*3 haplotype] underwent a fat load test consisting of the consumption of 1 g of fat per kilogram body weight and 60,000 IU vitamin A. Blood samples were taken at time 0, at every hour until the sixth hour, and at every 2.5 h until the 11th hour. Total plasma cholesterol (C) and TG, and C, TG, apolipoprotein B-100, apolipoprotein B-48, and retinyl palmitate in lipoprotein fractions were determined. Results: Subjects with the APOA5*2 and APOA5*3 haplotypes had a higher area under the curve of total plasma TG (P = 0.03), large TG-rich lipoprotein (TRL)-TG (P = 0.02), small TRL-TG (P = 0.04), small TRL-C (P = 0.04), large TRL-C (P = 0.03), and small apolipoprotein B100 (P = 0.04) than subjects with the APOA5*1 haplotype. Conclusions: Our findings show that the presence of the APOA5*2 and APOA5*3 haplotypes in the APOA5 gene is associated with a higher postprandial response that could be involved in the higher risk of coronary heart disease associated with the 56G and −1131C alleles

Effects of rs7903146 variation in the Tcf7l2 gene in the lipid metabolism of three different populations.

TCF7L2 rs7903146 is an important genetic factor predicting type 2 diabetes (T2DM) which has also been linked to higher cardiovascular risk. To date, there is little information about the additional impact of this single nucleotide polymorphism (SNP) beyond glucose metabolism.We studied whether rs7903146 influenced postprandial lipid metabolism in three different populations (healthy young men, metabolic syndrome (MetS) patients and elderly persons). Eighty-eight healthy males were submitted to a single saturated fatty acid-rich test meal. Additionally, 110 middle-aged MetS patients and 20 healthy elderly persons (≥ 65 years) were submitted to three different dietary models followed by test meals. Minor allele homozygotes for rs7903146 showed a worse postprandial lipemia profile in young males, as seen by a lower HDL-cholesterol and Apo A1 concentration during the postprandial lipemia and a trend towards higher triglycerides (TG), than the other genotypes. In healthy elderly persons, carriers of the minor allele showed higher total cholesterol, LDL-cholesterol, Apo B and TG in the fasting state, and a higher postprandial area under the curve for total cholesterol, Apo B, small-triglyceride rich lipoprotein (TRL) cholesterol and small-(TRL) triglycerides. These results were accompanied by differential changes in adipokines. We did not observe any influence of rs7903146 on the postprandium of MetS patients.Healthy young males and elderly persons who are carriers of the mutant allele for rs7903146 have an impaired postprandial lipid metabolism that may be mediated by an alteration in adipokine regulation, and may be related to the higher cardiovascular risk observed in these persons.ClinicalTrials.gov NCT00429195

Correction: Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study).

[This corrects the article DOI: 10.1371/journal.pone.0153096.]

Baseline characteristics of the participants in the three studies depending on the TCF7L2 rs7903146 SNP.

<p>Chol: total cholesterol. All values are means ±S.E.</p>*<p>p<0,05 TT vs CT/CC;</p>**<p>p<0.05 CC vs CT/TT. Adjusted by age and BMI (all cohorts), diet and gender (Metabolic syndrome and aged cohorts), and center of origin (Metabolic Syndrome).</p

AUC of the different lipid particles in the elderly persons cohort under the dominant model assumption (min^*mg/dL)/10³.

*<p>p<0.05 CC vs CT/TT. All values are mean ±S.E. Adjusted by diet, age, gender and BMI.</p

AUC of the different lipid particles in the young male cohort (min^*mg/dL)/10³.

*<p>p<0.05 TT vs CT and TT vs CC.</p>**<p>p<0.05 TT vs CT. All values are mean±S.E. Adjusted by age and BMI.</p

AUC of the different lipid particles in the metabolic syndrome cohort under the dominant model assumption (min*mg/dL)/10³.

<p>All values are mean ±S.E. Adjusted by diet, age, gender, BMI and center of origin.</p

Plasma concentration of adiponectin (Panel A), leptin (Panel B) and resistin (Panel C) depending on the rs7903146 genotype.

<p>*p<0.05 CC vs CT/TT.</p