HLA structure of the Sardinian population: A haplotype study of 551 families

A study on the HLA structure of the Sardinian population was carried out on 551 healthy unrelated families representing all of the island districts. Altogether 2202 HLA-A, B, Cw, DR individual haplotypes and 853 different haplotypes were determined. Cavalli-Sforza and Edwards' genetic distance index for the total of 62 tested alleles showed a modest heterogeneity between one district and another (0.09-0.16). The genetic distance between Sardinians and the rest of the Italian population was 0.23 (0.22-0.26) and progressively increased in comparisons with caucasoids (0.26), negroids (0.34) and mongoloids (0.41). Sixty-three two-locus haplotypes with a high positive linkage disequilibrium were observed in our family sample. The percentages of two-locus haplotypes in LD shared with other populations turned out to be 45% with caucasoids, 20% with negroids and 10% with mongoloids. The distribution of the A, B, Cw, DR haplotypes is shown with 673 of them represented only once or twice, and 10 (1.2%) 14-322 times each. Of the latter, 8 are extended haplotypes, 6 of which characterize the Sardinian population. The analysis of our data suggests that the present-day Sardinian population is the result of a superposition of different populations, mainly consisting of caucasoids on a pre-caucasoid paleo-Mediterranean substratum.     

Genetic susceptibility to multiple sclerosis in Sardinians: an immunological study

Objectives - We studied the in vitro production of variably MS-related cytokines from Sardinian MS and healthy donors bearing the two "Sardinian" MS-associated HLA-DR alleles: DR3 and DR4 , with the purpose to evidentiate possible differences in their immune response. Materials and methods - ELISA were used for detection of cellular products by mitogen-activated peripheral blood mononuclear cells. Results - PHA-activated HLA-DR4+/DR3- mononuclear cells produce significantly higher amounts of TNF-α compared with the DR3 +/DR4- , In addition, homozygous HLA-DR3+ mononuclear cells from MS patients produce significantly lower amounts of IL-10 than those from homozygous HLA-DR3+ healthy donors. Conclusion - The abnormal production of detrimental or regulatory cytokines may account for the genetic susceptibility to MS in different HLA-subgroups of Sardinian MS patients.     

Evolution of the Dietary Patterns across Nutrition Transition in the Sardinian Longevity Blue Zone and Association with Health Indicators in the Oldest Old

Health and longevity in humans are influenced by numerous factors, including lifestyle and nutrition. However, the direct relationship between lifetime eating habits and functional capacity of the elderly is poorly understood. This study investigated the dietary changes across nutrition transition (NT) in the early 1960s, in a population located in the Sardinia island known for its longevity, dubbed as “Longevity Blue Zone” (LBZ), as well as the relationship between the dietary patterns and a panel of health indicators. A total of 150 oldest-old participants (89 women and 61 men, age range 90–101 years) living in the LBZ were recruited. Participants were interviewed using validated questionnaires to assess the consumption frequency of common food items, as well as the correlation with self-rated health, comorbidity, affective and cognitive level, physical mobility, disability and anthropometric parameters. Differences between subgroups were evaluated using the Mann-Whitney U test for independent samples or the Wilcoxon signed-rank test for paired samples. Correlation analysis was performed by calculating the Spearman correlation coefficient, separately in males and females. Compared to the pre-NT epoch, the consumption of meat, olive oil and fresh fruit slightly increased, while the consumption of lard, legumes and vegetables decreased. A significant association was found between increased olive oil intake across NT and self-rated health (ρ = 0.519), mobility (ρ = 0.502), improved vision (ρ = −0.227) and hearing (ρ = −0.314); increased chicken meat intake and performance in activities of daily living (basic activities of daily living: ρ = 0.351; instrumental activities of daily living: ρ = 0.333). Instead, vegetable consumption showed low correlation with health indicators. A mild increase in meat intake, mostly pastured poultry, is associated with better physical performance in the Sardinian LBZ elders, suggesting that a supply of protein may have been crucial to maintaining adequate functional capacity.     

ReviewDoes the “Hygiene Hypothesis” Provide an Explanation for the High Prevalence of Multiple Sclerosis in Sardinia?

The “hygiene hypothesis” describes a hypothetical scenario in which the balance between T^H1 (defending host against bacterial and viral infections) and T^H2 (defending against parasitic infections) immune responses is pivotal and in which the consequence of reducing the infectious stressors during infancy is increased autoimmunity (T^H1-mediated) and allergy (T^H2-mediated). Many epidemiological observations confirm that allergic and autoimmune diseases are significantly increased in the “developed” countries and negatively associated with childhood infections. However, it has been recently revealed that immune elements associated with allergy are extensively involved also in the pathogenesis of autoimmune demyelination and that T^H2- and T^H1-mediated infections ameliorate the course of the disease confirming that the allergic root is also responsible for the escalation of autoimmune disorders, and both have a common immunological denominator.

In the Italian island of Sardinia, MS and type-I diabetes frequencies have sharply increased in the last decades compared to other populations living in the same Mediterranean area. Initial observation led us to believe that environmental changes favoured the MS risk rise, thus sustaining the hygiene hypothesis. However, data on MS prevalence distribution in this territory suggest that other mechanisms than environment have also to be taken into great account. Our recent epidemiological studies reveal significant differences in the MS prevalence between rural and urban areas within the same province of Sassari but, contrarily to what expected from the hygiene hypothesis, MS prevalence is significantly higher in rural, genetically “archaic”, areas where the westernalization process has been less pronounced. On this basis we believe that, beside hygiene-related factors, genetics could represent a more relevant determinant of Sardinian high susceptibility to MS.