Giuseppina Marino

Low‐density‐lipoprotein peak particle size in a Mediterranean population

Background The predominance of small, dense low‐density lipoprotein (LDL) particles (‘LDL phenotype B’) has been associated with a three‐fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned.

Leukocyte count, diabetes mellitus and age are strong predictors of stroke in a rural population in southern Italy: an 8-year follow-up

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.

Liver is not the unique site of synthesis of β2-glycoprotein I (apolipoprotein H) : evidence for an intestinal localization

Apolipoprotein H is a protein of about 50 kilodaltons, structurally related to the regulators of the complement activation family. Its physiological function is poorly understood but it has been implicated in lipid metabolism and coagulative pathways. The major site of synthesis is thought to be the liver. Several reports indicate that apolipoprotein H is the antigen of the antiphospholipid antibodies and also behaves as an acute-phase reactant. Moreover, 40% of plasma apolipoprotein H is associated with very low-density lipoprotein, high-density lipoprotein, and postprandial chylomicrons. In this study we investigated other sites of synthesis by reverse transcription/polymerase chain reaction and we found apolipoprotein H mRNA expression in intestinal cell lines and tissues. Immunohistochemistry was performed on various fresh and paraffin-embedded tissues and apolipoprotein H was immunolocalized in the cytoplasm of hepatocytes and epithelial cells from colon and jejunum. This study indicates that apolipoprotein H is expressed at both mRNA and protein levels in enterocytes.

Serum apolipoprotein profile of hypertriglyceridemic patients with chronic renal failure on hemodialysis: A comparison with type IV hyperlipoproteinemic patients

Thirty-three patients with chronic renal failure (CRF) and uremic hypertriglyceridemia (HTG) on hemodialysis were compared with 33 type IV hyperlipoproteinemic patients matched for age, body mass index (BMI), and triglyceride (TG) levels. The two forms of hypertriglyceridemia showed different apolipoprotein profiles: apo AI, AII, and B levels and apo CII:CIII and TG:apo CIII ratios of CRF-HTG patients were lower and apo CIII levels were higher than the levels of type IV subjects.

Apolipoprotein profile in type II diabetic patients with and without coronary heart disease

SummaryDiabetes mellitus is frequently associated with lipid metabolism abnormalities. In the present study the lipid and apolipoprotein profiles have been compared in type II diabetic subjects with (n=30) and without (n=30) coronary heart disease (CHD). All subjects were studied after good metabolic control had been achieved. Significant differences in plasrna lipids and apolipoproteins were seen in diabetic patients with CHD in comparison with diabetics without CHD. Patients with CHD presented higher total cholesterol, triglyceride, LDL-cholesterol, apo B, apo CII and apo CIII levels and total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios and lower HDL-cholesterol values and apo AI/o B ratio than the patients without CHD. The same findings were found in females; while male subjects with CHD had significantly increased total cholesterol, LDL-cholesterol and apo B levels and total cholesterol/HDL-cholesterol and LDL/cholesterol/HDL-cholesterol ratios and significantly decreased apo AI/o B ratio compared with males without CHD. These findings support the concept that the apolipoprotein profile plays a remarkable role as risk factor for CHD in type II diabetes mellitus.

Differential apolipoprotein(a) isoform expression in heterozygosity is an independent contributor to lipoprotein(a) levels variability.

BACKGROUND AND METHODS Lipoprotein(a) [Lp(a)] levels represent an independent risk factor for cardio- and cerebrovascular diseases. Since lipoprotein(a) levels show a wide variability even in subjects with similar apolipoprotein(a) isoforms, we investigated the contribution of apolipoprotein(a) heterozygosity to lipoprotein(a) variance. Lipoprotein(a) levels, apolipoprotein(a) isoforms identification and expression, and the correlation with other lipo-apolipoprotein parameters have been investigated in 628 subjects >18 years of age. RESULTS In our study, 246 subjects were found heterozygous for apolipoprotein(a) isoforms. Lipoprotein(a) levels were higher in females. About 40% of the subjects expressed the larger isoform more intensely than the dominant isoform. Lipoprotein(a) was correlated with apolipoprotein(a) dominant isoform size, HDL-cholesterol and smaller apolipoprotein(a) isoform expression rate. Lipoprotein(a) was independently correlated with the smaller apolipoprotein(a) isoform, with its expression rate and with LDL-cholesterol. The inclusion of the smaller apolipoprotein(a) expression rate in a multiple regression model explained at least an additional 4% of the lipoprotein(a) variance after correction for apolipoprotein(a) size. CONCLUSIONS The smaller isoforms are not always effectively dominant in heterozygosis since 40% of the subjects expressed more the larger isoform. The individual variability of apolipoprotein(a) isoform expression in heterozygosis could explain part of the lipoprotein(a) levels variability.

Rapid screening of the LDL receptor point mutation FH-Genoa/Palermo

The LDL‐receptor gene point mutation FH‐Genoa/Palermo is the most frequent mutation responsible for Familial Hypercholesterolemia in Sicily. The mutation does not introduce or abolish any useful restriction site. We establish a GeneComb™‐based strategy to identify this mutation in a population of Sicilian unrelated clinically diagnosed FH probands. The method was very sensitive and specific; 12 out of 90 (13.3%) unrelated FH probands were found to carry the FH‐Genoa/Palermo mutation. According to these results, the FH‐Genoa/Palermo is the more frequent LDL‐receptor gene mutation among the Sicilian FH patients. Moreover FH‐Genoa/Palermo is the mutation cluster to date more represented in Southern Italy. Hum Mutat 13:412–412, 1999.

Fibrinogen and von Willebrand factor in type II diabetes mellitus

A hypercoagulable state may contribute to the formation of early vascular lesions in diabetes. The von Willebrand factor is required for the attachment of platelets to the subendothelium; fibrinogen is required for platelet aggregation. This study was designed to assess in type II diabetic patients plasma levels of fibrinogen and von Willebrand factor to see if these variables are associated with platelet aggregation responses to adenosine diphosphate (ADP). Fibrinogen and the von Willebrand factor were significantly increased in diabetics but only fibrinogen was significantly related to platelet aggregation for ADP. Strict metabolic control does not reduce the increased concentrations of these two proteins. Hyperfibrinogenaemia was related to the presence of macrovascular disease. Therefore measurements of plasma fibrinogen could be added to the cardiovascular risk factor profile of diabetic patients. Intervention studies are also needed to reduce the increased incidence of thrombotic diseases in patients with diabetes mellitus.

Rapid screening of the LDL receptor point mutation FH-Genoa/Palermo. Mutation in brief no. 238. Online.

Type 2 (non‐insulin dependent) diabetes mellitus may be inherited along the maternal line and a variety of mitochondrial DNA (mtDNA) variants have been implicated in the pathogenesis. We have previously reported mutations in five regions of the mitochondrial genome which encompass 11 of the 22 tRNA genes. Now we employ the technique of single stranded conformational polymorphism (SSCP) analysis to investigate a further 6 regions of the mitochondrial genome, covering the remaining 11 tRNA genes in 40 patients with Type 2 diabetes and 30 racially‐matched normal controls. A variety of homoplasmic mutations were detected in patients with diabetes and these will be of value in further population association studies. Hum Mutat 13:412–413, 1999.

Lipid and Apoprotein Profile in Renal Transplant Recipients

Lipid and apoprotein profiles of renal transplant recipients were compared with that of a group of uremic patients on hemodialytic treatment. Total cholesterol, HDL-cholesterol, apo AI and apo B were higher and triglycerides, apo CII, apo CIII and apo E lower in renal transplant patients. Type IIa and IIb were the prevalent phenotypes in renal transplant recipients.