Glucagon receptor Gly40Ser amino acid variant in Sardinian hypertensive non-insulin-dependent diabetic patients

A significantly different prevalence in the Gly40Ser variant of the glucagon receptor gene in a small group of essential hypertensive patients compared with normotensive probands was described in a Caucasian population. It has been postulated that this variant may exacerbate the antinatriuretic effect of high plasma insulin levels commonly seen in hypertensive subjects, leading to volume expansion and rise in blood pressure level. The aim of this study was to evaluate the prevalence of the Gly40Ser variant in a population of 404 non-insulin-dependent diabetic patients of Sardinian origin. No association of the Gly40Ser variant with hypertension was seen in this large population. Received: 10 September 1996 / Accepted in revised form: 5 February 1997     

Immunogenetic heterogeneity of multiple sclerosis in Sardinia

Multiple sclerosis (MS) predisposition is thought to be influenced by a complex, yet unclear interaction of genetic and environmental factors. Studying ethnically selected populations may reduce genetic and environmental heterogeneities and help clarify the underlying mechanisms of MS susceptibility. Sardinians kept a homogeneous genetic structure and have among the highest MS frequency rates worldwide. Interestingly, MS in Sardinia is linked to otherwise rare HLA alleles. In this light, recent findings from epidemiological and immunogenetic studies of Sardinian MS are presented. Results confirm that, likely due to significant genetic differences at a microgeographic level, even in this homogeneous population MS is immunogenetically heterogeneous and tends to preferentially cluster in some more archaic areas of the island.     

High frequency of the TARDBP p.Ala382Thr mutation in Sardinian patients with amyotrophic lateral sclerosis

Recently, rare mutations in the TARDBP gene have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to characterize the genetic variability of the TARDBP gene in a cohort of Sardinian ALS patients. The coding region of the gene was analyzed in 97 unrelated patients previously tested negative for superoxide dismutase (SOD1) mutations. The p.Ala382Thr (c.1144G>A) mutation was found in 30 patients (30.9%). The mutation was predominant in familial ALS patients (FALS) as it was represented in 24 of 30 FALS cases (80%) (p < 0.0003). Six cases were apparently sporadic (9% of sporadic ALS patients). No further mutation of TARDBP was found in our cohort of ALS patients. Patients carrying the mutation showed spinal site of onset in 24 cases (80%), an average age at onset of 54.7 ± 11.1 years, not significantly different from patients not harboring TARDBP mutations (56.7 ± 9.6) and a female:male gender ratio of 1:1.1. The haplotype analysis carried out using eight microsatellite markers flanking the gene showed a founder effect for this mutation. Finally, we estimated the age-specific penetrance of the TARDBP p.Ala382Thr mutation in an additional sample of 47 carriers (20 affected and 27 unaffected). The average penetrance to 70 years was 60% (95% confidence interval 41-79%). A trend toward a higher penetrance in males was observed. Even in the presence of a causal mutation, most of the ALS clinical heterogeneity, however, draws upon from a multifactorial context.     

Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia

AIM:To investigate the role of protein tyrosin phosphatase 22(PTPN22),maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes(T1D)in Continental Italy and Sardinian populations.METHODS:Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia.PTPN22 genotype was determined by DNA analysis.Maternal age at conception and age at onset of disease were obtained from clinical records.χ2 test of independence,student t test for differences between means and odds ratio analysis were carried out by SPSS programs.Three way contingency table analysis was carried out according to Sokal and Rohlf.RESULTS:The pattern of association between PTPN22and T1D is similar in Continental Italy and Sardinia:the proportion of*T allele carriers is 13.6%in T1D vs6.7%in controls in Continental Italy while in Sardinia is 7.3%in T1D vs 4.4%in controls.The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy:the proportion of newborn from mother aging more than 32 years is89.3%in T1D vs 32.7%in consecutive newborn in Sardinia(P10-6)while in Continental Italy is 32.2%in T1D vs 19.1%in consecutive newborns(P=0.005).This points to an important role of ethnicity.A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia.PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia.Maternal age does not influence significantly age at onset in Italy(8.2 years in T1D infants from mothers aging32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years:P=0.824)while in Sardinia a border line effect is observed(5.75 years in T1D infants from mothers aging 32 years or less vs7.54 years in T1D infants from mothers aging more than 32 years:P=0.062).No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males(8.07 years in males vs 6.3 years in females:P=0.002).CONCLUSION:The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.     

Analysis of 12,517 inhabitants of a Sardinian geographic isolate reveals that predispositions to thrombocytopenia and thrombocytosis are inherited traits

Background

Thrombocytopenia is a common finding in several diseases but almost nothing is known about the prevalence of thrombocytopenia in the general population. We examined the prevalence of thrombocytopenia and determinants of platelet count in a healthy population with a wide age range.

Design and Methods

We performed a cross-sectional study on 12,517 inhabitants of ten villages (80% of residents) in a secluded area of Sardinia (Ogliastra). Participants underwent a complete blood count evaluation and a structured questionnaire, used to collect epidemiological data.

Results

We observed a platelet count lower than 150×10⁹/L in 3.2% (2.8%–3.6%) of females and 4.8% (4.3%–5.4%) of males, with a value of 3.9% (3.6%–4.3%) in the entire population. Thrombocytopenia was mild (platelet count: 100×10⁹/L–150×10⁹/L), asymptomatic and not associated with other cytopenias or overt disorders in most cases. Its standardized prevalence was quite different in different villages, with values ranging from 1.5% to 6.8%, and was negatively correlated with the prevalence of a mild form of thrombocytosis, which ranged from 0.9% to 4.5%. Analysis of platelet counts across classes of age revealed that platelet number decreased progressively with aging. As a consequence, thrombocytopenia was nearly absent in young people and its prevalence increased regularly during lifetime. The opposite occurred for thrombocytosis.

Conclusions

Given the high genetic differentiation among Ogliastra villages with “high” and “low” platelet counts and the substantial heritability of this quantitative trait (54%), we concluded that the propensity to present mild and transient thrombocytosis in youth and to acquire mild thrombocytopenia during aging are new genetic traits.     

Extensive Nosocomial Transmission of Measles Originating in Cruise Ship Passenger,Sardinia, Italy, 2014

We report a measles outbreak in Sardinia, Italy, that originated in a cruise ship passenger. The outbreak showed extensive nosocomial transmission (44 of 80 cases). To minimize nosocomial transmission, health care facilities should ensure that susceptible health care workers are vaccinated against measles and should implement effective infection control procedures.     

Classic Kaposi's sarcoma in southern Sardinia, Italy

The first examination of classical Kaposi's sarcoma incidence in southern Sardinia (Italy) in 1998-2002 found the highest rate recorded in the island of 2.49 per 100 000 per year (standardised).     

Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk

OBJECTIVES: To update prevalence and incidence rates of MS among Sardinians. MATERIALS AND METHODS: The present work is a "spider" kind of population based survey, conducted over the interval 1968-97, on patients with MS (Poser criteria) living in the province of Sassari, Northern Sardinia (454,904 population). RESULTS: A crude total prevalence rate of 144.4 per 100,000, an onset-adjusted prevalence rate of 149.7 per 100,000 and an average annual incidence rate of 8.2 for the period 1993-7 were found. CONCLUSION: Repeated epidemiological assessments of MS in Sardinia over decades have shown that the island is at high risk for MS. The present work highlights that MS incidence in Sardinia has been increasing over time. Although a substantial and widely spread improvement in MS case ascertainment can be postulated as the reason for such observations, a comparison between our data and those recently reported from a more industrialized province in Northern Italy seems to prove an at least partially real increase in MS risk among Sardinians and favours the hypothesis of a MS "Sardinian focus" as related to its latitude.