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S Muntoni

Publications and source records attributed to S Muntoni.

At least 19 recordsLinked to original sources
PubMed1997

Incidence of insulin-dependent diabetes mellitus among Sardinian-heritage children born in Lazio region, Italy.

BACKGROUND: The relative importance of genetic and environmental factors in causing insulin-dependent diabetes mellitus (IDDM) is unknown. We studied this question by assessing the incidence of the disease in children, born in a region with a low incidence of IDDM (Lazio), but whose parents came from a region with high incidence (Sardinia). METHODS: We identified all IDDM cases that occurred between 1989 and 1994. We used as the denominator the number of children aged 0-14 born in Lazio of Sardinian parents to calculate incidence. We compared this rate with the incidences of IDDM in the populations of Lazio and Sardinia. FINDINGS: The age-adjusted incidence of IDDM in Sardinian-heritage children born and living in Lazio was 33.8 per 100,000 per year (95% CI 7.0-99.0) for those with two Sardinian parents, and 15.9 (8.7-26.6) for those with only one parent from Sardinia. The former incidence was not different from that recorded in Sardinia (34.4, 31.3-37.9), but was fourtold that of Lazio-heritage children (7.9, 7.1-8.8). INTERPRETATION: Our results show that two different ethnic groups living in the same region have a fourfold difference in incidence of IDDM. Children of Sardinian-heritage born in Lazio have the same incidence as the population of origin, which is genetically prone to the disease. Moreover, children with one Sardinian parent had a rate half that of Sardinians and double that of the indigenous population. We conclude that in a given population genetic susceptibility determines the frequency of IDDM in response to the environmental challenge.

Adolescent↗
PubMed1996

A missense mutation (Thr-6Pro) in the lysosomal acid lipase (LAL) gene is present with a high frequency in three different ethnic populations: impact on serum lipoprotein concentrations.

A frequent missense mutation (Thr-6Pro) found in the prepeptide of the lysosomal acid lipase (LAL) gene was analyzed in a cohort of 1003 randomly selected samples from Germany, Japan and Sardinia (Italy). Using the mutagenically separated polymerase chain reaction (MS-PCR), allele frequencies of 0.269, 0.238 and 0.245 were determined in the three populations, respectively. Statistical analysis showed a lack of association with a dyslipidemic phenotype in all three groups. Additionally, in a subgroup of 126 German individuals no association was observed between genotype and LAL activity. We conclude that this mutation appears to be a frequent LAL gene polymorphism causing no impaired function of the enzyme and no measurable dyslipidemia in the general population.

Base Sequence↗
PubMed1995

Homozygosity for a splice junction mutation in exon 8 of the gene encoding lysosomal acid lipase in a Spanish kindred with cholesterol ester storage disease (CESD).

Deficiency of lysosomal acid lipase is expressed in two distinct recognizable phenotypes. Wolman disease represents the severe early onset form, whereas cholesterol ester storage disease is the more benign late onset type. Previous studies have indicated that compound heterozygosity consisting of a G-->A mutation at the 3'-splice junction of exon 8 (E8SJM-allele) together with a null allele of the gene encoding lysosomal acid lipase leads to cholesterol ester storage disease. We have now observed homozygosity for the G-->A splice junction mutation in a non-related Spanish kindred with the same disease. As expected, the residual activity of lysosomal acid lipase is higher in this case, suggesting that the E8SJM-allele is associated with low residual acid lipase activity. However, the phenotype of the homozygous propositus is more severe compared with the previously described case, indicating that no direct relationship exists between the genotype or residual LAL activity and the precise cholesterol or triglyceride levels in a given patient. Nevertheless, our findings provide convincing evidence that homozygosity for the E8SJM-allele causes cholesterol ester storage disease to at least the same extent as compound heterozygosity consisting of this allele and a null allele.

Adult↗
PubMed1995

Prevention of cardiovascular disease: from biomedical research to health policy.

Cardiovascular diseases (CVD) are the leading cause of premature death and disability in the developed world. Broad consensus exists on CVD preventability through reduction of their risk factors at both the individual and population level. The latter kind of intervention implies involvement of policy-making institutions, owing to the manifold implications (agriculture, industry, environment) of such programmes. They have to be developed through three phases in succession: observational studies; intervention trials; public health action programmes. The implementation of the latter can only result from merging of biomedicine and politics and must rest on sound scientific-ethical bases. Other important issues are cost effectiveness, resort to mass media, transfer to other communities, funding and institutionalization. As a practical example of development and implementation of a public health programme, the experience of the ATS-Sardegna Campaign is briefly described.

Cardiovascular Diseases↗
PubMed1995

A novel variant of lysosomal acid lipase (Leu336-->Pro) associated with acid lipase deficiency and cholesterol ester storage disease.

Cholesterol ester storage disease (CESD) is associated with premature atherosclerosis, hepatomegaly, elevated LDL cholesterol levels, and in most cases, low HDL cholesterol levels. Previous studies have shown a G-->A mutation at the 3' splice junction of exon 8 (E8SJM) of the gene encoding lysosomal acid lipase (LAL) in two kindreds with CESD. In a Canadian-Norwegian kindred with this disease, we show this mutation in conjunction with an as yet unknown T-->C transition in exon 10 predicting a Leu336-->Pro (L336P) replacement and an A-->C transversion in exon 2 predicting a T-6P replacement in the prepeptide. Identification of the L336P rather than the T-6P replacement as the second defect underlying CESD in our patient is deduced from three lines of evidence. First, the E8SJM allele is located in cis with the mutation predicting the T-6P-encoding allele but in trans with the L336P-encoding allele; second, the L336P but not the T-6P replacement cosegregates with low LAL activity in the family; third, the T-6P replacement was found in 6 of 28 alleles from subjects with normal lysosomal acid lipase activity, suggesting that this variant represents a frequent nonfunctional polymorphism. Since the residual LAL activity is higher and the clinical phenotype based on plasma lipid values and severity of hepatosplenomegaly is milder in this case than in a previously studied case who was homozygous for the E8SJM allele, we conclude that the L336P variant appears to be associated with a phenotypically mild form of CESD.

Adult↗
PubMed1995

Steadily high IDDM incidence over 4 years in Sardinia.

OBJECTIVE: To verify whether the high incidence of insulin-dependent diabetes mellitus (IDDM) in Sardinia is an epidemic outbreak or a steady phenomenon. RESEARCH DESIGN AND METHODS: All newly diagnosed cases of IDDM with onset in patients 0-29 years of age between 1 January 1989 and 31 December 1992 among residents in Sardinia were obtained from the Sardinian IDDM Incidence Registry. The local IDDM patient association (Associazione Diabete Infantile Giovanile) served as the secondary and independent source. RESULTS: The completeness of ascertainment was 91%. The age-standardized mean annual incidence of IDDM (per 100,000) was 34.4 in the 0- to 14-year-old age-group and 26.2 in the entire 0- to 29-year-old range, respectively. Men-to-women ratios were 1.38 and 1.55, respectively. Seasonal variation in incidence was observed, with a peak in fall and winter and a nadir in summer. CONCLUSIONS: Sardinia has a very high and steady IDDM incidence rate, which is up to fivefold that of other Italian regions and Mediterranean countries and approaches the Finnish top rate in the world. Interaction between the genetic peculiarity of Sardinians and still unidentified powerful environmental agents is likely to account for the phenomenon.

Adolescent↗
PubMed1994

Decrease of thyroid hormones in patients with familial hypercholesterolemia during dextran sulphate low-density lipoprotein apheresis.

Removal of low-density lipoproteins from plasma by dextran sulfate adsorption (DSA) in FH patients entails a decrease in plasma levels of thyroid hormones (-28.5% and -18.7%, respectively, for T3 and T4). This suggests that FH patients have a greater than normal fraction of thyroid hormones bound to lipoproteins, due to their expanded lipoprotein pool.

Adolescent↗
PubMed1993

Increasing prevalence of juvenile onset type 1 (insulin-dependent) diabetes mellitus in Sardinia: the military service approach.

In order to obtain new and more detailed information about temporal trends and geographic distribution of Type 1 (insulin-dependent) diabetes mellitus in Sardinia, we screened a series of birth cohorts (1936-1973) of all male army conscripts aged 18-19 years, filed in the Sardinian Conscript Register where Type 1 diabetes is a cause of rejection. A total of 678 diabetic subjects, born and permanently residing in Sardinia, was identified. The point prevalence (x 1000) at the age of 20 years in the birth cohorts ranged from values close to zero for the first ten cohorts (1936-1945) up to a maximum of 3.08 (95% confidence limits 2.28-4.08) for the 1966 cohort and continued high thereafter although an apparent decrease was observed from the early 1970s birth cohorts. Type 1 diabetes was distributed throughout the four provinces of Sardinia with no particularly significant heterogeneity; however, in accordance with the geographical distribution of diabetes cases of the Eurodiab Ace survey (1989-1990), the highest prevalence of the disease was observed in the Cagliari and Oristano provinces, followed by Nuoro and Sassari. These data suggest a gradually increasing trend of male Type 1 diabetes prevalence in Sardinia with a 29-fold increase between the late 1930s and the late 1960s birth cohorts. This seems to confirm the high incidence of Type 1 diabetes in the 0-14 and 0-29 year age groups recently reported among Sardinians during the Eurodiab Ace collaborative multicentre study.

Adolescent↗
PubMed1992

Serum lipoprotein profile in the Mediterranean variant of glucose-6-phosphate dehydrogenase deficiency.

Sardinian males with erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency have lower serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB), compared to normals. Since the enzyme deficiency is expressed also in nucleated cells, we studied cholesterol (C) and DNA synthesis and LDL-receptor expression in freshly isolated circulating mononuclear cells from normal and G-6-PD-deficient Sardinians. Synthesis of C (as 14C-acetate incorporation) and of DNA (as 3H-thymidine incorporation) was clearly reduced, both in basal state and after PHA stimulation, in G-6-PD-deficient cells compared to normal cells. On the other hand, no clear influence of G-6-PD deficiency on LDL-receptor expression could be demonstrated. The Mediterranean variant of G-6-PD deficiency is characterized, whatever the metabolic mechanism may be, by a serum lipoprotein pattern of reduced atherogenicity.

Adult↗
PubMed1992

The HLA DQB1*0502 allele is neutrally associated with insulin-dependent diabetes mellitus in the Sardinian population.

In the Sardinian population a very high incidence of insulin-dependent diabetes mellitus (IDDM) and the lack of HLA-DR2 protective effect due to the high frequency of the A2, Cw7, B17, 3F31, DR2, DQw1 extended haplotype has been reported. This haplotype, carrying a Serine at position 57 of the DQB1*0502 allele, has been previously reported to be underrepresented in patients when compared to controls. In order to provide an explanation for this finding, we defined by RFLP analysis the HLA haplotype of 45 Sardinian IDDM patients and 49 controls. All DR-2DQw1 subjects were molecularly characterized at the HLA DQA and DQB loci. All DR2-positive patients and the vast majority of the DR2-positive controls had the DQB1*0502 allele at the DR2-linked DQB1 locus, with no statistically significant difference between the two groups. All DQA1 genes were the ones expected, with only two exceptions. Nine out of 10 of the DR2-positive patients were compound heterozygotes for DQB1*0201/DQB1*0502 alleles; only this allele combination was significantly increased (p less than 0.0003). Our data suggests that a) the DQB1*0502 allele is neutral for IDDM development and b) the susceptibility to IDDM in our DR2-positive patients is related to the compound heterozygous state between the neutral DQA1*0102/DQB1*0502 and the susceptibility DQA1*0501/DQB1*0201 alleles.

Adolescent↗
PubMed1992

High incidence rate of IDDM in Sardinia. Sardinian Collaborative Group for Epidemiology of IDDM.

OBJECTIVE: To provide reliable data on the incidence of IDDM in Sardinia and contribute to a better understanding of its geographical variability throughout Europe. RESEARCH DESIGN AND METHODS: All newly diagnosed cases of IDDM with onset less than 30 yr of age between 1 January 1989 and 31 December 1990 among residents in Sardinia were recorded. Primary ascertainment was based on notification by all Sardinian hospitals, outpatient clinics, family doctors, and pediatricians. The local IDDM patient association served as the secondary and independent source. RESULTS: The completeness of ascertainment was 92.8%. The annual incidence rate of IDDM (per 100,000) over the 2-yr period was 30.7 in the 0-14-yr-old age-group and 24.1 in the entire 0-29-yr-old range, respectively, with no significant differences between the two groups. Male/female ratios were 1.25 and 1.55, respectively. No significant seasonal variation in incidence was observed. CONCLUSIONS: Sardinia appears to have the second-highest IDDM incidence rate in Europe after Finland, and the island contradicts the generally accepted rule of a south-to-north incidence gradient.

Adolescent↗
PubMed1992

Serum lipoprotein pattern as modified in G6PD-deficient children during haemolytic anaemia induced by fava bean ingestion.

In the present study, plasma lipid concentrations were determined at different times after admission in sera from G6PD-deficient children during haemolytic crisis induced by fava bean ingestion. Reductions in total, LDL and HDL cholesterol were found in association with the maximum of bone marrow hyperplasia. A return towards normal values occurred with regression of the disease. No changes in other lipid parameters were observed. These data suggest that alterations of lipoprotein pattern, other than in experimental animals, are also present in humans with non-malignant proliferative processes. These changes appear to be a consequence of the disease, probably due to an increased utilization of cholesterol by proliferating cells.

Anemia, Hemolytic↗
PubMed1991

Mean levels and distribution of some risk factors for atherosclerosis in Sardinia: the ATS-Sardegna Survey.

Six population samples of randomly chosen men and women aged 20-59 years in the four provinces of the island of Sardinia, for a total of 5,697 individuals (overall participation 55%), were examined to determine the mean levels and distribution of some risk factors for atherosclerosis. A remarkable uniformity of such levels, with some minor exceptions, was found throughout the island. The overall, age-standardized mean levels for the factors considered are as follows (men and women, respectively): total cholesterol (TC) (mg/dl) 204 and 196; LDL-cholesterol (LDL-C) (mg/dl) 131 and 125; apolipoprotein B (ApoB) (mg/dl) (five out of six areas) 112 and 104; HDL-cholesterol (HDL-C) (mg/dl) 48 and 53; triglyceride (TG) (mg/dl) 117 and 89; systolic blood pressure (mmHg) 129 and 128; diastolic blood pressure (mmHg) 81 and 80; body mass index (BMI) [kg/(m)2] 26 and 25; prevalence of smokers (%) 48 and 15; cigarettes per day among smokers 19 and 11. A regular increase with increasing age exists for TC, LDL-C, ApoB, blood pressure (systolic and diastolic) and BMI. Compared to the results of a previous survey eight years earlier, an unfavorable trend is in progress, particularly for TC levels in both sexes and smoking among women.

Adult↗