HERV-W and Mycobacterium avium subspecies paratuberculosis Are at Play in Pediatric Patients at Onset of Type 1 Diabetes

The etiology of T1D remains unknown, although a variety of etiological agents have been proposed as potential candidates to trigger autoimmunity in susceptible individuals. Emerging evidence has indicated that endogenous human retrovirus (HERV) may play a role in the disease etiopathogenesis; although several epigenetic mechanisms keep most HERVs silenced, environmental stimuli such as infections may contribute to the transcriptional reactivation of HERV-Wand thus promote pathological conditions. Previous studies have indicated that also Mycobacterium avium subspecies paratuberculosis (MAP) could be a potential risk factor for T1D, particularly in the Sardinian population. In the present study, the humoral response against HERV-W envelope and MAP-derived peptides was analyzed to investigate their potential role in T1D etiopathogenesis, in a Sardinian population at T1D onset (n = 26), T1D (45) and an age-matched healthy population (n = 45). For the first time, a high serum-prevalence of anti-Map and anti-HERV-W Abs was observed in pediatric patients at onset of T1D compared to T1D patients and healthy controls. Our results support the hypothesis that external infections and internal reactivations are involved in the etiology of T1D, and that HERV-W activation may be induced by infectious agents such as MAP.

Does the longevity of the Sardinian population date back to Roman times? A comprehensive review of the available evidence

The discovery early in this century of the exceptional longevity of the Sardinian population has given new impetus to demographic studies of this phenomenon during the classical period. In the 1970s, it was hypothesised that the average mortality rate in Roman Sardinia was lower than in metropolitan Rome itself, postulating an ancient precedent for the remarkable longevity observable nowadays in the island’s population. In the present study, the available evidence was examined in order to test this hypothesis. Literary, juridical, epigraphic, papyrological, anthropological and archaeological sources regarding the population of the Roman Empire, including Sardinia, were retrieved by accessing Science Direct, PubMed, Scopus and Google Scholar databases, as well as regional libraries, regardless of time limitation, and were independently reviewed by the authors. For Roman Sardinia, only funerary epitaphs were retrieved, in contrast with the numerous sources available for the whole Roman Empire. Inscriptions revealing the existence of three alleged nonagenarians, two centenarians, two ultracentenarians and one supercentenarian were found, corresponding to 2% in a total of 381 inscriptions. The majority were located in a highly Romanised rural area of central-western Sardinia. However, the ages reported in the epitaphs may be inaccurate because of the influence of confounders such as age rounding, approximations and/or amplifications, and are unrelated to the total number of inhabitants. In conclusion, the funerary evidence, the only available data from Roman Sardinia, is too weak to estimate the life expectancy of the local ancient population and cannot offer valuable arguments to support the hypothesis that exceptional longevity has been a Sardinian trait since Roman times.

Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience

AimSARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome.Method and MaterialsWe recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies.ResultsMale sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8–8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7–220.6), Pc = 0.024].ConclusionThe data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.

Haemolymphatic cancer among children in Sardinia, Italy: 1974–2003 incidence

ObjectivesTo explore the time trend and geographical distribution of childhood leukaemia incidence over the territory of the Italian region of Sardinia.SettingAll hospitals departments, diagnostic centres and social security agencies in Sardinia were regularly screened in 1974–2003 to identify, register and review the diagnoses of incident cases of haematological malignancies (HM).ParticipantsThe whole child population aged 0–14 resident in Sardinia.Primary and secondary outcome measuresIncidence and time trend of childhood HM and childhood acute lymphoblastic leukaemia (ALL) over the study period, and use of Bayesian methods to plot the probability of areas with excess incidence on the regional map.ResultsOverall, 675 HM cases, including 378 ALL cases, occurred among children aged 0–14 years resident in Sardinia in 1974–2003, with an incidence rate of 6.97×10-5 (95% CI 6.47 to 7.51) and 3.85×10-5 (95% CI 3.48 to 4.26), respectively. Incidence of HM and ALL showed an upward trend along the study period especially among females. Three communes out of the 356 existing in 1974, namely Ittiri, Villa San Pietro and Carbonia, stand out as areas with excess incidence of HM and ALL in particular and another, Carloforte, for ALL only.ConclusionsOur results might serve as convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants in the areas at risk.

A Genetic Window on Sardinian Native Horse Breeds through Uniparental Molecular Systems

Sardinia, an island located to the west of Italy in the Mediterranean Sea, boasts three native horse breeds: Giara, Sarcidano, and Sardinian Anglo-Arab. Here, we have investigated for the first time three loci of the non-recombining region of the Y chromosome (NRY) in 34 stallions from these breeds and performed a phylogenetic analysis of the maternal relationships among 178 previously published mitochondrial control regions. We found that the current NRY diversity of Sardinian horse breeds is linked to three haplotypes (HT), all identified within Sarcidano. Each breed showed a typical HT: HT1 (ancestral) was the most represented in Sarcidano, HT2 (Neapolitan/Oriental wave) in Giara, and HT3 (Thoroughbred wave) in Sardinian Anglo-Arab. The specificity of each haplotype suggests the influence of independent breeding strategies and the effect of genetic drift in each Sardinian population. The female counterpart, extended to 178 horses, showed a low genetic variability and a common maternal origin for Giara and Sarcidano. The higher variability of the Sardinian Anglo-Arab indicates multiple mare lineages in its current population. Further genetic analyses will be crucial to understand the paternal history of male horses, preserve the endangered mares’ and stallions’ lineages, and improve the enhancement of autochthonous genetic resources on this island.

Genetic Characterization of Endometriosis Patients: Review of the Literature and a Prospective Cohort Study on a Mediterranean Population

The pathogenesis of endometriosis is unknown, but some evidence supports a genetic predisposition. The purpose of this study was to evaluate the recent literature on the genetic characterization of women affected by endometriosis and to evaluate the influence of polymorphisms of the wingless-type mammalian mouse tumour virus integration site family member 4 (WNT4), vezatin (VEZT), and follicle stimulating hormone beta polypeptide (FSHB) genes, already known to be involved in molecular mechanisms associated with the proliferation and development of endometriotic lesions in the Sardinian population. Materials and Methods: In order to provide a comprehensive and systematic tool for those approaching the genetics of endometriosis, the most cited review, observational, cohort and case-control studies that have evaluated the genetics of endometriosis in the last 20 years were collected. Moreover, 72 women were recruited for a molecular biology analysis of whole-blood samples—41 patients affected by symptomatic endometriosis and 31 controls. The molecular typing of three single nucleotide polymorphisms (SNPs) was evaluated in patients and controls: rs7521902, rs10859871 and rs11031006, mapped respectively in the WNT4, VEZT and FSHB genes. In this work, the frequency of alleles, genotypes and haplotypes of these SNPs in Sardinian women is described. Results: From the initial search, a total of 73 articles were chosen. An analysis of the literature showed that in endometriosis pathogenesis, the contribution of genetics has been well supported by many studies. The frequency of genotypes observed in the groups of the study population of 72 women was globally coherent with the law of the Hardy–Weinberg equilibrium. For the SNP rs11031006 (FSHB), the endometriosis group did not show an increase in genotypic or allelic frequency due to this polymorphism compared to the control group (p = 0.9999, odds ratio (OR) = 0.000, 95% confidence interval (CI), 0.000–15.000 and p = 0.731, OR = 1639, 95% CI, 0.39–683, respectively, for the heterozygous genotype and the polymorphic minor allele). For the SNP rs10859871 (VEZT), we found a significant difference in the frequency of the homozygous genotype in the control group compared to the affected women (p = 0.0111, OR = 0.0602, 95% CI, 0.005–0.501). For the SNP rs7521902 (WNT4), no increase in genotypic or allelic frequency between the two groups was shown (p = 0.3088, OR = 0.4133, 95% CI, 0.10–1.8 and p = 0.3297, OR = 2257, 95% CI, 0.55–914, respectively, for the heterozygous genotype and the polymorphic minor allele). Conclusion: An analysis of recent publications on the genetics of endometriosis showed a discrepancy in the results obtained in different populations. In the Sardinian population, the results obtained do not show a significant association between the investigated variants of the genes and a greater risk of developing endometriosis, although several other studies in the literature have shown the opposite. Anyway, the data underline the importance of evaluating genetic variants in different populations. In fact, in different ethnic groups, it is possible that specific risk alleles could act differently in the pathogenesis of the disease.