SORT1 Protective Allele is Associated with Attenuated Postprandial Lipaemia in Young Adults
Background—Elevated levels of lipids and lipoproteins have strong genetic determinants, and are recognized as key risk factors for atherogenesis and cardiovascular disease (CVD), particularly in the postprandial state. Study aims were to determine if young adults, when stratified by genotype at the rs646776 variant of the 1p13 locus, displayed differential postprandial responses to an oral fat tolerance test.
Methods and Results—Participants (n=30) received a high fat mixed meal (91 g, 55% kcal from fat) following an overnight fast and a fat-exclusion meal (3.9 g, 6% kcal from fat) at 8 h postprandially. Blood samples were obtained at t=0, 2, 4, 6, 8 and 24 h for lipoprotein analyses via nuclear magnetic resonance profiling. Carriers of the minor, protective allele (TC/CC) displayed lower fasting (TC/CC: 30.1 ± 3.0 nM vs. TT: 48.8 ± 5.1 nM, p < 0.01) and mean postprandial (TC/CC: 44.2 ± 3.1 nM vs. TT: 57.0 ± 4.5 nM, p=0.03) very-low density lipoprotein and chylomicron particle number in addition to triglyceride content compared to individuals homozygous for the major, risk allele (TT).
Conclusions—We report a novel association between the SORT1 1p13 locus and extent of postprandial lipaemia. These results provide evidence of decreased exposure to atherogenic particles in carriers of the minor SORT1 allele, suggesting relative protection against CVD compared to TT homozygotes.
- Received February 7, 2014.
- Revision received May 23, 2014.
- Accepted June 4, 2014.