Search

We describe a Sicilian family presenting a recessive form of hypercholesterolemia harboring a mutation of the autosomal recessive hypercholesterolemia (ARH) gene. In two of the three sibs, a 26-year-old male and a 22-year-old female, a severe hypercholesterolemia was diagnosed with very high levels of plasma cholesterol (15.9 and 12.2 mmol/l, respectively); tendon xanthomatas and xanthelasms were present and in the male proband was documented a diffuse coronary atherosclerotic disease with a rapid and fatal progression. Both the parents had normal or slightly increased levels of plasma cholesterol. All causes of secondary hypercholesterolemia were ruled out as well as an involvement of the LDL receptor or apoB genes. Beta-Sitosterol plasma levels were in the normal range. Cultured fibroblasts from skin biopsy from parents and the two probands displayed a normal ability to bind and degrade 125I-LDL. Direct sequencing of ARH gene demonstrated the presence of a 432insA mutation in homozygosis in the two probands; parents were heterozygotes for the same mutation. This mutation is the first report of a mutation of the ARH gene responsible for recessive forms of hypercholesterolemia in Sicily.

Stroke incidence rates in the Mediterranean area are higher compared to northern European countries. In this study, we present the 8-year prospective data from a small rural Sicilian town. This population, consisting of 1351 subjects (622 males and 729 females), is homogeneous for ethnic background with traditional healthy dietary habits and shows low cholesterol mean levels. We found that the risk of stroke was significantly associated with the record of at least one previous neurological symptom (PNS), such as lack of strength, loss of vision or speech or possible drop attacks, and high hematocrit in males, and to high body mass index (BMI) and waist-hip ratio (WHR), diabetes, hypertension, high leukocyte count in females. We also documented age-related differences: stroke was associated in younger subjects (age<65 years) with diabetes, high BMI, high uric acid levels and in older patients (age>/=65 years) with high WHR, hypertension, diabetes, PNS, leukocyte count and hematocrit above the 95th percentile. Multivariate analysis demonstrated an independent association between stroke and age, diabetes, leukocyte count, hypertension and PNS. In conclusion, in this rural Sicilian population, the incidence rate of stroke is 1.72 cases per 1000/year in the subjects between 40 and 75 years of age. The risk factors associated with stroke are different in younger and older subjects. Leukocyte count, as an expression of an undergoing inflammatory process, may have a relevant role at least in the elderly.

An increased susceptibility of platelets to aggregation induced by various agents and a higher production of active arachidonate metabolism have been described in type IIa hypercholesterolemia. This study was designed to evaluate whether changes in platelet function could be observed in hypercholesterolemic patients after synvinolin therapy. Administration of synvinolin to 12 type IIa hypercholesterolemic patients for 24 weeks had a lipid lowering effect and resulted in a marked reduction of platelet aggregation and thromboxane formation induced by collagen and arachidonate. Maximum response was achieved at 4-8 weeks and lipid lowering effects at 2 weeks. This finding indicates that platelet changes cannot be explained by a direct effect of synvinolin on platelets, and the antiplatelet response may therefore depend on platelet membrane lipid composition changes, particularly in the platelet cholesterol content of platelet membranes, following substantial reductions of total plasma cholesterol and LDL-cholesterol.