In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 20, No. 1 ( 2000-01), p. 236-243
Abstract:
Abstract —One of the genetic features of the Sardinian population is the high prevalence of hemoglobin disorders. It has been estimated that 13% to 33% of Sardinians carry a mutant allele of the α-globin gene (α-thalassemia trait) and that 6% to 17% are β-thalassemia carriers. In this population, a single mutation of β-globin gene (Q39X, β 0 39) accounts for 〉 95% of β-thalassemia cases. Because previous studies have shown that Sardinian β-thalassemia carriers have lower total and low density lipoprotein (LDL) cholesterol than noncarriers, we wondered whether this LDL-lowering effect of the β-thalassemia trait was also present in subjects with familial hypercholesterolemia (FH). In a group of 63 Sardinian patients with the clinical diagnosis of FH, we identified 21 unrelated probands carrying 7 different mutations of the LDL receptor gene, 2 already known (313+1 g 〉 a and C95R) and 5 not previously reported (D118N, C255W, A378T, T413R, and Fs572). The 313+1 g 〉 a and Fs572 mutations were found in several families. In cluster Fs572, the plasma LDL cholesterol level was 5.76±1.08 mmol/L in subjects with β 0 -thalassemia trait and 8.25±1.66 mmol/L in subjects without this trait ( P 〈 0.001). This LDL-lowering effect was confirmed in an FH heterozygote of the same cluster who had β 0 -thalassemia major and whose LDL cholesterol level was below the 50th percentile of the distribution in the normal Sardinian population. The hypocholesterolemic effect of β 0 -thalassemia trait emerged also when we pooled the data from all FH subjects with and without β 0 -thalassemia trait, regardless of the type of mutation in the LDL receptor gene. The LDL-lowering effect of β 0 -thalassemia may be related to (1) the mild erythroid hyperplasia, which would increase the LDL removal by the bone marrow, and (2) the chronic activation of the monocyte-macrophage system, causing an increased secretion of some cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-α) known to affect the hepatic secretion and the receptor-mediated removal of apolipoprotein B–containing lipoproteins. The observation that our FH subjects with β 0 -thalassemia trait (compared with noncarriers) have an increase of blood reticulocytes (40%) and plasma levels of interleukin-6 (+60%) supports these hypotheses. The lifelong LDL-lowering effect of β 0 -thalassemia trait might slow the development and progression of coronary atherosclerosis in FH.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.20.1.236
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2000
detail.hit.zdb_id:
1494427-3
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