Article

Confirmation of the DRB1-DQB1 loci as the major component of IDDM1 in the isolated founder population of Sardinia.

Dipartimento di Scienze Biomediche e Biotecnologie, University of Cagliari, Via Jenner, Cagliari 09121, Italy.
Human Molecular Genetics (Impact Factor: 7.69). 01/2001; 9(20):2967-72. DOI: 10.1093/hmg/9.20.2967
Source: PubMed

ABSTRACT There is considerable uncertainty and debate concerning the application of linkage disequilibrium (LD) mapping in common multifactorial diseases, including the choice of population and the density of the marker map. Previously, it has been shown that, in the large cosmopolitan population of the UK, the established type 1 diabetes IDDM1 locus in the HLA region could be mapped with high resolution by LD. The LD curve peaked at marker D6S2444, 85 kb from the HLA class II gene DQB1, which is known to be a major determinant of IDDM1. However, given the many unknown parameters underlying LD, a validation of the approach in a genetically distinct population is necessary. In the present report we have achieved this by the LD mapping of IDDM1 in the isolated founder population of Sardinia. Using a dense map of microsatellite markers, we determined the peak of LD to be located at marker D6S2447, which is only 6.5 kb from DQB1. Next, we typed a large number of SNPs defining allelic variation at functional candidate genes within the critical region. The association curve, with both classes of marker, peaked at the loci DRB1-DQB1. These results, while representing conclusive evidence that the class II loci DRB1-DQB1 dominate the association of the HLA region to type 1 diabetes, provide empirical support for LD mapping.

1 Bookmark
 · 
52 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously reported a high prevalence (22.3%) of gestational diabetes mellitus (GDM) in a large group of Sardinian women, in contrast with the prevalence of Type 2 diabetes. Sardinia has an unusual distribution of haplotypes and genotypes, with the highest population frequency of HLA DR3 in the world, and after Finland, the highest prevalence of Type 1 diabetes and Autoimmune-related Diseases. In this study we preliminarily tested the prevalence of serological markers of Type 1 diabetes in a group of Sardinian GDM patients. We determined glutamic decarboxylase antibodies (anti-GAD65), protein tyrosine phosphatase ICA 512 (IA2) antibodies (anti-IA2), and IAA in 62 GDM patients, and in 56 controls with matching age, gestational age and parity. We found a high prevalence and very unusual distribution of antibodies in GDM patients (38.8%), the anti-IA2 being the most frequent antibody. Out of all our GDM patients, 38.8% (24 of 62) were positive for at least one antibody. Anti-IA2 was present in 29.0 % (18 out of 62) vs. 7.1% (4 out of 56) in the controls (P < 0.001). IAA was present in 14.5% (9 out of 62) of our GDM patients, and absent in the control subjects (P < 0.001). Anti-GAD65 was also present in GDM patients, with a prevalence of 3.2% (2 out of 62) while it was absent in the control group (P = NS). Pre-gestational weight was significantly lower (57.78 +/- 9.8 vs 65.9 +/- 17.3 P = 0.04) in auto-antibodies- positive GDM patients. These results are in contrast with the very low prevalence of all antibodies reported in Italy. If confirmed, they could indicate that a large proportion of GDM patients in Sardinia have an autoimmune origin, in accordance with the high prevalence of Type 1 diabetes.
    Reproductive Biology and Endocrinology 01/2008; 6:24. · 2.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Complex multifactorial disorders usually arise in individuals genetically at risk in the presence of permissive environmental factors. For many of these diseases, predisposing gene variants are partly known while the identification of the environmental component is much more difficult. This study aims to investigate whether there are correlations between the incidence of two complex traits, multiple sclerosis and type 1 diabetes, and some chemical elements and compounds present in soils and stream sediments in Europe. Data were obtained from the published literature and analyzed by calculating the mean values of each element and of disease incidence for each Country, respectively, 17 for multiple sclerosis and 21 for type 1 diabetes. Correlation matrices and regression analyses were used in order to compare incidence data and geochemical data. R correlation index and significance were evaluated. The analyses performed in this study have revealed significant positive correlations between barium and sodium oxide on one hand and multiple sclerosis and diabetes incidences on the other hand that may suggest interactions to be evaluated between silicon-rich lithologies and/or marine environments. The negative correlations shown by cobalt, chromium and nickel (typical of silicon-poor environment), which in this case can be interpreted as protective effects against the two diseases onset, make the split between favorable and protective environments even more obvious. In conclusion, if other studies will confirm the involvement of the above elements and compounds in the etiology of these pathologies, then it will be possible to plan strategies to reduce the spread of these serious pandemics.
    Environmental Geochemistry and Health 04/2013; · 2.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In Romagna Apennines 770 stream sediment samples were collected and analysed for 30 elements by X-ray fluorescence spectometry on the fraction < 180μm. In the area industrial settlements and largest towns are in the plains and agricultural areas in the hills: these anthropogenic activities cause the dispersion of polluting substances into environment and the assessment of anomalous values of certain elements such as Cu, Pb, S, Zn, V, Cr and Ni especially along the valleys. Identifying the spatial distribution and the background value of these chemical elements are the primary step in environmental monitoring for facilitating the decision-making process. The spatial variability may be represented by geochemical maps which allow a better visualization of the geochemical changes in a given area. This case study compares two techniques: IDW interpolation and Sample Catchment Basin (SCB) mapping approach. Background values and anomalies derive from processes that are space-dependent, thus the task is to display these different processes in map form and to detect local deviations from the dominating process in any one sub-area. Because multiple processes are involved, this may appear close to impossible at first glance. However, by splitting the data into groups on the basis of univariate statistical techniques it is possible to display the spatial aspects of the data structure in a map. Therefore this database is been processed using EDA analysis, percentiles, boxplot and cumulative probability plot. Studying geochemical maps carried out by GIS elaboration and observing poly-populational data distributions in chemical elements, we prove that concentrations are controlled by geological and anthopogenic factors. This fact is related to the different types of polluting dispersion: for example geochemical maps of Zn, S and Cu obtained by IDW interpolation point out areas with a broad pollution derived from lithological substrate and valleys with circumscribed anomalies due to anthopogenic activities. Comparing the same elements with a geochemical map obtained by catchment basins, we note that the identification of source areas is also powerful because are outlined the boundary of anomalies based on land physiography. Considering the importance of real background values in environmental management, different threshold values between anomalies derived by geological and anthropogenic factors have been applied: the resulting class divisions have been used in geochemical maps and show an objective distribution and extension of chemical element anomalies related to polluting substances.
    Geoitalia 2013, Pisa; 09/2013

Full-text (2 Sources)

View
2 Downloads
Available from
Jun 10, 2014