The -1131T>C SNP of the APOA5 gene modulates response to fenofibrate treatment in patients with the metabolic syndrome: a postprandial study.
OBJECTIVE
Apolipoprotein A5 is a key gene controlling VLDL synthesis and hydrolysis and is the target of the main pharmacological agent to lower triglycerides (fibrates). We hypothesised that variability in the promoter of the APOA5 gene may affect the individual response to fibrate therapy, in both the fasting and postprandial states.


METHODS
We selected 50 subjects with the metabolic syndrome who also had important increase in fasting triglycerides. A subgroup of 36 patients underwent lipid-lowering treatment with 160 mg/day of fenofibrate (Secalip) for 3 months. The participants underwent a 60 g fat overload with a commercial preparation, after which we assessed the influence of the -1131T>C APOA5 SNP on the postprandial response.


RESULTS
Compared with non-carriers, the C allele carriers had significantly higher triglyceride levels at baseline (54.87%), and at 3h (61.08%) and 4h (68.35%). Other lipid parameters were not affected by the APOA5 genotype. Our results indicate that carriers of the -1131C allele had a better response to fenofibrate treatment (reduction in triglyceride levels of 40.33% at baseline, P=0.018; and postprandially, 37.64% at 3h, P=0.028 and 42.58% at 4h after the high-fat meal, P=0.018) than wild-type subjects (30.91% decrease at baseline, P<0.001; and 26.61% at 3h P=0.005 and 22.95% at 4h P=0.033 after the high-fat meal).


CONCLUSIONS
Thus, the treatment for patients with the metabolic syndrome and elevated plasma triglyceride levels may vary according to whether they carry the APOA5 -1131T>C polymorphism.
Servicio de Endocrinología y Nutrición, Hospital Virgen de la Victoria, Málaga, Malaga, Spain. fernandocardonadiaz@gmail.com
Fernando
F
Cardona
Montserrat
M
Guardiola
María Isabel
MI
Queipo-Ortuño
Mora
M
Murri
Josep
J
Ribalta
Francisco J
FJ
Tinahones
D000328:Adult; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D004041:Dietary Fats; D008055:Lipids; D014280:Triglycerides; D011345:Fenofibrate