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 FindingsWe 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/SignificanceHealthy 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
Highlights
Postprandial lipemia is characterized as a period by an increase in proinflammatory and prooxidant species in the bloodstream, along with a transient increase in some lipid fractions with direct pro-atherogenic properties, such as small triglyceride-rich lipoproteins (TRL)
We recently reported how a variation of the rs7903146 gene is linked to a dysfunction in glucose metabolism during the postprandial state in metabolic syndrome (MetS) patients, without affecting fasting glucose or insulin, and mainly influencing markers of beta-cell function, such as those associated to insulin secretion [17]
Our study shows that carriers of the rare allele of TCF7L2 rs7903146 have a disrupted lipid metabolism, which is seen in different ways depending on age and baseline conditions
Summary
Postprandial lipemia is characterized as a period by an increase in proinflammatory and prooxidant species in the bloodstream, along with a transient increase in some lipid fractions with direct pro-atherogenic properties, such as small triglyceride-rich lipoproteins (TRL). Several studies have linked the extent of this state to the development of coronary heart disease [1,2,3]. Several diseases have been recognized as powerful modifiers of postprandial lipemia, such as type 2 diabetes (T2DM), and metabolic syndrome (MetS). These two conditions present an altered lipid metabolism, with increased triglyceride levels and increased postprandial lipemia, along with lower HDL levels and a proatherogenic LDL phenotype consisting of smaller and denser molecules. There is little information about the additional impact of this single nucleotide polymorphism (SNP) beyond glucose metabolism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
