Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men.
The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism, we studied the effects of nine single nucleotide polymorphisms (SNPs) during postprandial lipid metabolism. Eighty-eight healthy young men were genotyped for APOA1 -2630 (rs613808), APOA1 -2803 (rs2727784), APOA1 -3012 (rs11216158), APOC3 -640 (rs2542052), APOC3 -2886 (rs2542051), APOC3 G34G (rs4520), APOA4 N147S (rs5104), APOA4 T29T (rs5092), and A4A5_inter (rs1263177) and were fed a saturated fatty acid-rich meal (1g fat/kg of weight with 60% fat, 15% protein and 25% carbohydrate). Serial blood samples were extracted for 11 h after the meal. Total cholesterol and fractions [HDL-cholesterol, LDL-cholesterol, trifacylglycerols (TGs) in plasma, TG-rich lipoproteins (TRLs) (large TRLs and small TRLs), apolipoprotein A-I and apolipoprotein B] were determined. APOA1 -2803 homozygotes for the minor allele and A4A5_inter carriers showed a limited degree of postprandial lipemia. Carriers of the rare alleles of APOA4 N147S and APOA4 T29T had lower APOA1 plasma concentration during this state. APOC3 -640 was associated with altered TG kinetics but not its magnitude. We have identified new associations between SNPs in the APOA1/C3/A4/A5 gene cluster and altered postprandial lipid metabolism.
Delgado-Lista
Javier
J
Lipids and Atherosclerosis Research Unit, Reina Sofía University Hospital, Instituto Maimonides de Investigación Biomedica de Cordoba (IMIBIC), University of Cordoba, Ciber Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, CordobaSpain.
Perez-Jimenez
Francisco
F
Ruano
Juan
J
Perez-Martinez
Pablo
P
Fuentes
Francisco
F
Criado-Garcia
Juan
J
Parnell
Laurence D
LD
Garcia-Rios
Antonio
A
Ordovas
Jose M
JM
Lopez-Miranda
Jose
J
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics*; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000097:blood / Q000235:genetics*; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics*; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D005227:Fatty Acids / Q000378:metabolism; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D005810:Multigene Family; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
C505693:APOA1 protein, human; C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D005227:Fatty Acids; D014280:Triglycerides; C022205:apolipoprotein A-IV; D002784:Cholesterol