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DOI: 10.1055/s-2004-861495
β-Thalassemia Is a Modifying Factor of the Clinical Expression of Familial Hypercholesterolemia
Publikationsverlauf
Publikationsdatum:
03. Januar 2005 (online)
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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, β-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 β-thalassemia due to a single mutation (Q39X) of the β-globin gene that abolishes the synthesis of β-globin chain of hemoglobin (β°-thalassemia). Plasma LDL-C in FH heterozygotes carrying the β°-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, β-thalassemia trait may protect FH heterozygotes against premature coronary atherosclerosis.
KEYWORDS
Familial hypercholesterolemia - low-density lipoproteins - β-thalassemia - cardiovascular risk - LDL receptor
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Dr.
Sebastiano Calandra
Department of Biomedical Sciences, University of Modena & Reggio Emilia
Via Campi 287, 41100 Modena, Italy