A common polymorphism in the fatty acid transport protein-1 gene associated with elevated post-prandial lipaemia and alterations in LDL particle size distribution.
The fatty acid transport proteins (FATPs) have been implicated in facilitated cellular uptake of non-esterified fatty acids (NEFAs), thus having the potential to regulate local and systemic NEFA concentrations and metabolism. Hypothesising that genetic variation within the FATP genes may affect lipid metabolism, we investigated a G/A substitution at position 48 in intron 8 of the fatty acid transport-1 (FATP1) gene with respect to associations with fasting and post-prandial plasma lipid and lipoprotein variables in 628 healthy 50-year-old Swedish men and 426 Swedish women, aged 37-65 years. A subset of 105 men with the apoE3/E3 genotype underwent an oral fat tolerance test. Although fasting plasma TG concentrations were not different, male A/A individuals had significantly higher post-prandial TG concentrations and VLDL(1) (S(f) 60-400 apoB100)-to-VLDL(2) (S(f) 20-60 apoB100) ratio compared to male G/A and G/G individuals. A/A individuals apparently failed to suppress plasma NEFA concentrations during the oral fat tolerance test. Furthermore, fasting plasma concentrations of the largest, most buoyant LDL subfraction (LDL-I) were significantly lower in carriers of the A allele in the male cohort. Electromobility shift assays and reporter gene studies indicated that binding of nuclear factors and effect on transcriptional activity differ between the intron 8 alleles. These findings suggest that through regulation of NEFA trafficking, FATP1 might play a role in post-prandial lipid metabolism and development of cardiovascular disease.
Gertow
K
K
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden. karl.gertow@medks.ki.se
Skoglund-Andersson
C
C
Eriksson
P
P
Boquist
S
S
Orth-Gomér
K
K
Schenck-Gustafsson
K
K
Hamsten
A
A
Fisher
R M
RM
D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D050612:Fatty Acid Transport Proteins; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000032:analysis / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D010316:Particle Size; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012737:Sex Factors
D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D005819:Genetic Markers; D008077:Lipoproteins, LDL; D026901:Membrane Transport Proteins; C493568:SLC27A1 protein, human