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

Pablo Perez-Martinez, Ana I Perez-Caballero, Antonio Garcia-Rios, Elena M Yubero-Serrano, Antonio Camargo, Maria J Gomez-Luna, Carmen Marin, Purificacion Gomez-Luna, Aldona Dembinska-Kiec, Fernando Rodriguez-Cantalejo, Francisco J Tinahones, Helen M Roche, Francisco Perez-Jimenez, Jose Lopez-Miranda, Javier Delgado-Lista, Pablo Perez-Martinez, Ana I Perez-Caballero, Antonio Garcia-Rios, Elena M Yubero-Serrano, Antonio Camargo, Maria J Gomez-Luna, Carmen Marin, Purificacion Gomez-Luna, Aldona Dembinska-Kiec, Fernando Rodriguez-Cantalejo, Francisco J Tinahones, Helen M Roche, Francisco Perez-Jimenez, Jose Lopez-Miranda, Javier Delgado-Lista

Abstract

Background: 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.

Methodology/principal findings: 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.

Conclusions/significance: 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.

Trial registration: ClinicalTrials.gov NCT00429195.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Plasma concentration of adiponectin (Panel…
Figure 1. Plasma concentration of adiponectin (Panel A), leptin (Panel B) and resistin (Panel C) depending on the rs7903146 genotype.
*p

Figure 2. Area under curve (AUC) of…

Figure 2. Area under curve (AUC) of Total Cholesterol and Apo B (Panel A), and…

Figure 2. Area under curve (AUC) of Total Cholesterol and Apo B (Panel A), and Small-TRL contained Cholesterol, TG and Apo B (Panel B) depending on the rs7903146 in aged cohort (mean
±S.E). *p<0.05 TT vs TC/TT. Values are in (min*mg/dL)/103.
Figure 2. Area under curve (AUC) of…
Figure 2. Area under curve (AUC) of Total Cholesterol and Apo B (Panel A), and Small-TRL contained Cholesterol, TG and Apo B (Panel B) depending on the rs7903146 in aged cohort (mean
±S.E). *p<0.05 TT vs TC/TT. Values are in (min*mg/dL)/103.

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