Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges.
The aim of this study was to investigate the influence of APOA5 variants on fasting lipids and to the response to both an oral fat tolerance test (OFTT) and an oral glucose tolerance test (OGTT). The association of two APOA5 SNPs [S19W (SNP5), -1131T>C (SNP3)] and an APOA4/A5 intergenic SNP [-12238T>C (SNP4)] were examined in healthy young men (n=774) who had undergone both an OFTT and an OGTT. Both -1131T>C and S19W rare alleles were associated with triglyceride (TG)-raising effects (11%, P=0.008; 21% (in cases), P<0.026, respectively) and showed additive effects on TG. None of the variants influenced the responsiveness to the OFTT after correcting for baseline TG. Homozygosity for the -12238T>C rare allele was associated with higher waist to hip ratio (P<0.0006), systolic blood pressure (P=0.012) and AUC and peak of insulin after OGTT (P=0.003 and P=0.027, respectively), traits that define the metabolic syndrome. Our results strongly support the role of APOA5 in determining plasma TG levels in an age-independent manner and highlight the importance of the APOC3/A4/A5 gene cluster in both TG and metabolic homeostasis.
Martin
Steve
S
Division of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University Street, WC1E 6JF, London, UK.
Nicaud
Viviane
V
Humphries
Steve E
SE
Talmud
Philippa J
PJ
D000328:Adult; D032721:Adult Children; D000483:Alleles; D000704:Analysis of Variance; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D004041:Dietary Fats / Q000008:administration & dosage; D005215:Fasting; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood*
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D014280:Triglycerides