Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia

Katherine K Anagnostopoulou,Dimitri P Mikhailidis,Genovefa D Kolovou,Christina Marvaki,Dimitrios Degiannis,Georgios Hatzigeorgiou,Peggy M Kostakou,Dennis V Cokkinos,Constantinos Mihas

doi:10.1186/1476-511x-8-24

Abstract

BackgroundThis study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia.MethodsWe selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h).ResultsIn the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup.ConclusionIn conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings.

Highlights

This study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia
In the subgroup heterozygotes for familial hypercholesterolaemia (hFH)-P, the presence of the B2 allele was significantly related to lower levels of TG-Areas under the curve (AUC) (p = 0.01), adjusting for age, gender and body mass index (BMI) (Table 6)
Sub grouping led to small study groups and a greater number of subjects are needed to draw definite conclusions. It seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein (CETP) gene were both associated with the distribution of TG values after oral fat tolerance test (OFTT), only in subjects with a pathological response to OFTT

Summary

Introduction

This study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia. When the levels of fasting [10,11,12] or postprandial [11,13] TG-rich lipoproteins are increased, CETP transfers HDL cholesteryl esters towards larger VLDL particles resulting in the formation of small dense LDL particles [9]. In type IIB hyperlipidaemia during the fasting state, CETP is implicated in the intravascular formation of atherogenic, small dense LDL through an indirect mechanism involving an elevated rate of cholesteryl esters transfer from HDL to VLDL and to large VLDL-1 particles [14]. Elevated levels of cholesteryl ester-enriched VLDL-1 are associated with enhanced formation of atherogenic, small dense LDL in hypertriglyceridaemic states and notably in hyperlipidaemias of phenotypes IIB and IV and in the dyslipidaemias of type 2 diabetes and metabolic syndrome [9]. Therapeutic strategies have been developed to influence the action of CETP [15]

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