{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T06:41:34Z","timestamp":1772952094591,"version":"3.50.1"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2000,1]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014One 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 \u03b1-globin gene (\u03b1-thalassemia trait) and that 6% to 17% are \u03b2-thalassemia carriers. In this population, a single mutation of \u03b2-globin gene (Q39X, \u03b2<jats:sup>0<\/jats:sup>39) accounts for &gt;95% of \u03b2-thalassemia cases. Because previous studies have shown that Sardinian \u03b2-thalassemia carriers have lower total and low density lipoprotein (LDL) cholesterol than noncarriers, we wondered whether this LDL-lowering effect of the \u03b2-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&gt;a and C95R) and 5 not previously reported (D118N, C255W, A378T, T413R, and Fs572). The 313+1 g&gt;a and Fs572 mutations were found in several families. In cluster Fs572, the plasma LDL cholesterol level was 5.76\u00b11.08 mmol\/L in subjects with \u03b2<jats:sup>0<\/jats:sup>-thalassemia trait and 8.25\u00b11.66 mmol\/L in subjects without this trait (<jats:italic>P<\/jats:italic>&lt;0.001). This LDL-lowering effect was confirmed in an FH heterozygote of the same cluster who had \u03b2<jats:sup>0<\/jats:sup>-thalassemia major and whose LDL cholesterol level was below the 50th percentile of the distribution in the normal Sardinian population. The hypocholesterolemic effect of \u03b2<jats:sup>0<\/jats:sup>-thalassemia trait emerged also when we pooled the data from all FH subjects with and without \u03b2<jats:sup>0<\/jats:sup>-thalassemia trait, regardless of the type of mutation in the LDL receptor gene. The LDL-lowering effect of \u03b2<jats:sup>0<\/jats:sup>-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-\u03b1) known to affect the hepatic secretion and the receptor-mediated removal of apolipoprotein B\u2013containing lipoproteins. The observation that our FH subjects with \u03b2<jats:sup>0<\/jats:sup>-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 \u03b2<jats:sup>0<\/jats:sup>-thalassemia trait might slow the development and progression of coronary atherosclerosis in FH.<\/jats:p>","DOI":"10.1161\/01.atv.20.1.236","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"236-243","source":"Crossref","is-referenced-by-count":24,"title":["Influence of \u03b2<sup>0<\/sup>-Thalassemia on the Phenotypic Expression of Heterozygous Familial Hypercholesterolemia"],"prefix":"10.1161","volume":"20","author":[{"given":"Luca","family":"Deiana","sequence":"first","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Garuti","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni Mario","family":"Pes","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciriaco","family":"Carru","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Errigo","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Rolleri","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Pisciotta","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Masturzo","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Cantafora","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastiano","family":"Calandra","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Bertolini","sequence":"additional","affiliation":[{"name":"From the Institute of Clinical Biochemistry (L.D., G.M.P., C.C., A.E.), University of Sassari, Sassari, Italy; the Department of Biomedical Sciences (R.G., S.C.), University of Modena, Modena, Italy; the Department of Internal Medicine (M.R., L.P., P.M., S.B.), University of Genoa, Genoa, Italy; and the National Institute of Health (A.C.), Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Goldstein JL Hobbs HH Brown MS. 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