title: Beta-thalassemia is a modifying factor of the clinical expression of familial hypercholesterolemia.
abstract: Familial hypercholesterolemia (FH) is a codominant disorder due to a variety of mutations of the low-density lipoprotein (LDL) receptor gene that result in an elevation of plasma LDL-cholesterol (LDL-C). Plasma levels of LDL-C show large interindividual variation even in subjects carrying the same mutation of the LDL receptor gene. This variability may be due to genetic factors (modifier genes). Several surveys indicate that the overall contribution of common polymorphisms of modifier genes (such as the genes encoding apolipoproteins E and B) to this variability is less than 10%. In contrast, beta-thalassemia has a profound LDL-lowering effect. This was documented in FH patients identified on the island of Sardinia, in Italy, where 12% of the inhabitants are carriers of beta-thalassemia due to a single mutation (Q39X) of the beta-globin gene that abolishes the synthesis of beta-globin chain of hemoglobin (beta(o)-thalassemia). Plasma LDL-C in FH heterozygotes carrying the beta(o)-thalassemia trait is 25% lower than in noncarriers, regardless of the LDL receptor gene mutation. It is likely that this effect is due to two main mechanisms: (1) increased uptake of LDL by the bone marrow to provide cholesterol for the increased proliferation of erythroid progenitor cells and (2) increased production of inflammatory cytokines that reduce the hepatic secretion and increase the catabolism of LDL. In view of its LDL-C-lowering effect, beta-thalassemia trait may protect FH heterozygotes against premature coronary atherosclerosis.
authors.affiliation: Department of Biomedical Sciences, University of Modena & Reggio Emilia, 4100 Modena, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
authors.forename: Giovanni Mario
authors.initials: GM
authors.lastname: Pes
authors.forename: Luca
authors.initials: L
authors.lastname: Deiana
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
authors.forename: Livia
authors.initials: L
authors.lastname: Pisciotta
authors.forename: Salvatore
authors.initials: S
authors.lastname: Li Volti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.forename: Carmela
authors.initials: C
authors.lastname: Maccarone
mesh_terms: D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000517:prevention & control; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000235:genetics*; D009154:Mutation; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: D002784:Cholesterol