Introduction. Mutations of the ANGPTL3 gene have been foundresponsible for a novel form of primary hypobetalipoproteinemia(pHBL), the combined hypolipidemia, characterized by low totalcholesterol (TC) and low HDL-cholesterol (HDL-C) levels. Theaim of this work is to define the role of ANGPTL3 gene as determinantof the combined hypolipidemia phenotype in two large cohortsof 913 American and Italian subjects with primary hypobetalipoproteinemia(TC <5th percentile).Materials and Methods. The cut-offs adopted to define the combinedhypolipidemia phenotype were chosen taking into accountthe TC and HDL-C levels reported in the ANGPTL3 kindred describedto date and are as follows: TC levels <2nd percentile andHDL-C levels <20th percentile. We selected seventy-eight subjectswith the combined hypolipidemia and analyzed the ANGPTL3 andthe APOB genes.Results. We identified nonsense and/or missense mutationsin ANGPTL3 gene in eight subjects; no mutations of the APOBgene were found in the seventy-eight subjects with the combinedhypolipidemia phenotype ANGPTL3 homozygous/compound heterozygoussubjects showed a more severe biochemical phenotypecompared to heterozygous or ANGPTL3-negative subjects withcombined hypolipidemia. Lipid profile of ANGPTL3 heterozyotesdid not differ from ANGPTL3-negative subjects.Conclusion. These results demonstrated that in a cohort of subjectswith severe pHBL the prevalence of ANGPTL3 gene mutationsresponsible of a combined hypolipidemia phenotype is high(about 10%) while mutations of APOB gene are absent.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2011|