Heterozygosity for lysosomal acid lipase E8SJM mutation and serum lipid concentrations.

BACKGROUND AND AIM: The complete absence of the lysosomal acid lipase (LAL) enzyme function causes Wolman's Disease that is fatal within the first six months of life. Subtotal defects cause Cholesteryl ester storage disease (CESD), an autosomal recessive disorder leading to hepatic steatosis, fibrosis, micronodular cirrhosis, combined hyperlipidemia with low HDL-cholesterol, increased risk for atherosclerosis, premature death. Since the frequency of the Exon 8 splice junction mutation (c.894 G > A, E8SJM), the CESD leading mutation, is not rare in the general population (allele frequency 0.0025), we investigated the impact of this mutation on serum lipid profile in E8SJM carriers. METHODS AND RESULTS: We collected E8SJM carriers both form genetic study-population analysis and from Outpatient Lipid Clinics and then we assessed their serum lipid profile. We found thirteen individuals heterozygote for E8SJM. Most of them were Germans, three Spanish and two Italian. We found a significant increase in total cholesterol levels in both sexes with E8SJM mutation, leading to a significant increase in LDL cholesterol in males. CONCLUSIONS: Our results show that LAL E8SJM carriers have an alteration in lipid profile with a Polygenic Hypercholesterolemia phenotype, leading to an increase in cardiovascular risk profile.

Prevalence of diagnosed and undiagnosed diabetes mellitus and impaired fasting glucose in Sardinia.

We aimed at updating the prevalence of impaired fasting glucose (IFG) and of undiagnosed (UD) and diagnosed diabetes (DD) among the Sardinian population. The survey was carried out from 2002 to 2005 on 4.737 subjects aged 20-80+ years. IFG was diagnosed when blood glucose was 110-125 mg/dl; UD when it was >or=126 mg/dl in the absence of personal history of diabetes; DD when personal history was positive, irrespective of blood glucose value. Prevalence rates (%) were adjusted for age by direct method to the Italian 2001 population. IFG was diagnosed in 11% of the sample (9.88% in females and 12.24% in males); UD was found in 5.65% (5.20 and 6.15%, females and males, respectively), DD in 8.72% (6.74 and 10.05%); and total diabetes (TD), i.e. the sum of UD + DD, was 14.37% (12.93 and 15.07%, females and males, respectively). In Sardinia, in about 5 years there was an increase of IFG (+61.8%), UD (+56.9%), DD (+55.7%), and TD (+57.9%). Thus Sardinia participates in the worldwide increase in prevalence of diabetes and its microvascular, macrovascular, and socioeconomic consequences.

Glucose-6-phosphate dehydrogenase deficiency protects against coronary heart disease.

Previous studies suggest a reduction in cardiovascular risk among subjects expressing the glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) deficient phenotype. We aimed to test this hypothesis in male subjects expressing the G6PD-deficient phenotype vs wild type G6PD. In a case-control study we examined consecutive patients admitted for acute myocardial infarction or unstable angina, and controls admitted for diagnoses other than coronary heart disease (CHD). The G6PD phenotype was determined by measuring the enzyme activity in erythrocytes, as the absorbance rate change due to NADPH reduction. The CHD risk associated with the G6PD phenotype was assessed with unconditional logistic regression. G6PD-deficient subjects were less frequently represented among cases (11.8%) than among controls (18.6%, p=0.002). The genetic condition of G6PD deficiency conveyed a significant reduction in CHD risk (OR=0.6; 95% CI 0.4 to 0.9). We confirm the hypothesis that subjects with the G6PD-deficient phenotype are less prone to CHD. We suggest that such a protective effect may be ascribable to a reduced 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA R) activity, a statin-like effect, as well as to a downregulation in NADPH oxidase activity with a consequent reduction in oxygen-free radical production.