The APOA5-1131 T>C variant enhances the association between RBP4 and hypertriglyceridemia in diabetes.
OBJECTIVE
Type 2 diabetic patients have an increased prevalence of hypertriglyceridemia. RBP4 has been associated with insulin resistance and hypertriglyceridemia in obesity, the metabolic syndrome and type 2 diabetes. APOA5 is proposed to be a genetic modulator of triglycerides. The aim of this study was to evaluate the relationship between RBP4 plasma levels and lipid disturbances and to determine the impact of the APOA5-1131 T>C variant on this relationship in type 2 diabetic patients.


RESULTS
A total of 165 type 2 diabetic patients were included in the study. RBP4 plasma levels and the APOA5-1131 T>C variant were determined and the complete lipid profile was assessed by sequential ultracentrifugation. RBP4 was positively correlated with triglyceride levels in plasma and with all the components of triglyceride-rich lipoproteins. Despite the fact that a statistically significant relationship between the APOA5 genetic variant and RBP4 plasma levels was not found, the hypertriglyceridemic effect of high RBP4 levels was enhanced by the presence of the APOA5-1131 T>C genetic variant. Correlation coefficients were 2-fold higher for TC carriers compared to TT carriers with regard to RBP4 plasma levels and all the components of triglyceride-rich lipoproteins. Those type 2 diabetic patients with high RBP4 plasma concentrations and who were TC carriers showed an increased incidence of hypertriglyceridemia (OR=7.46, P=0.010).


CONCLUSIONS
RBP4 is associated with hypertriglyceridemia in type 2 diabetic patients. The RBP4 effect is conditioned by the presence of the APOA5-1131 T>C genetic variant.
Cabré
A
A
CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), URV, Department of Internal Medicine, Sant Joan University Hospital, Reus, Spain.
Lázaro
I
I
Girona
J
J
Manzanares
J M
JM
Marimón
F
F
Plana
N
N
Guardiola
M
M
Heras
M
M
Masana
L
L
D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics* / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology* / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics* / Q000502:physiology; D014280:Triglycerides / Q000097:blood
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D008055:Lipids; D008074:Lipoproteins; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D014280:Triglycerides; D004247:DNA