http://www.cnr.it/ontology/cnr/individuo/prodotto/ID27452

Pro-inflammatory variants of DRB1 and RAGE genes are associated with susceptibility to pediatric type 1 diabetes: a new hypothesis on the adaptive role of autoimmunity. (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

Pro-inflammatory variants of DRB1 and RAGE genes are associated with susceptibility to pediatric type 1 diabetes: a new hypothesis on the adaptive role of autoimmunity. (Articolo in rivista) (literal)

Anno

2007-01-01T00:00:00+01:00 (literal)

Alternative label

Damiani, G (Damiani, Giuseppe); Campo, I (Campo, Ilaria); Zorzetto, M (Zorzetto, Michele); Bozzi, V (Bozzi, Valeria); Disabella, E (Disabella, Eliana); Caroli, A (Caroli, Anna); Ferrarotti, I (Ferrarotti, Ilaria); D'Annunzio, G (D'Annunzio, Giuseppe); Pasi, A (Pasi, Annamaria); Martinetti, M (Martinetti, Miryam); Cuccia, M (Cuccia, Mariaclara) (2007)
Pro-inflammatory variants of DRB1 and RAGE genes are associated with susceptibility to pediatric type 1 diabetes: a new hypothesis on the adaptive role of autoimmunity.
in Biology forum; Tilgher-Genova, Genova (Italia)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Damiani, G (Damiani, Giuseppe); Campo, I (Campo, Ilaria); Zorzetto, M (Zorzetto, Michele); Bozzi, V (Bozzi, Valeria); Disabella, E (Disabella, Eliana); Caroli, A (Caroli, Anna); Ferrarotti, I (Ferrarotti, Ilaria); D'Annunzio, G (D'Annunzio, Giuseppe); Pasi, A (Pasi, Annamaria); Martinetti, M (Martinetti, Miryam); Cuccia, M (Cuccia, Mariaclara) (literal)

Pagina inizio

285 (literal)

Pagina fine

304 (literal)

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100 (literal)

Rivista

Biology forum (Rivista)

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REVIEW (literal)

Note

ISI Web of Science (WOS) (literal)

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1. CNR, Ist Genet Mol Evolutionary Genet, I-27100 Pavia, Italy 2. IRCCS Policlin San Matteo, Clin Malattie Apparato Resp, Lab Biochim & Genet, Pavia, Italy 3. Univ Pavia, Dipartimento Med Interna, I-27100 Pavia, Italy 4. IRCCS Policlin San Matteo, Lab Area Trapiantol, Pavia, Italy 5. Univ Brescia, Dipartimento Sci Biomed & Biotecnol, I-25121 Brescia, Italy 6. Ist Giannina Gaslini, Pediat Clin, I-16148 Genoa, Italy 7. IRCCS Policlin S Matteo, Serv Immunoematol & Med Trasfus, Pavia, Italy 8. Univ Pavia, Dipartimento Genet & Microbiol, Immunogenet Lab, I-27100 Pavia, Italy (literal)

Titolo

Pro-inflammatory variants of DRB1 and RAGE genes are associated with susceptibility to pediatric type 1 diabetes: a new hypothesis on the adaptive role of autoimmunity. (literal)

Abstract

Functional polymorphisms of two MHC genes (DRB1 and RAGE) were analysed in Italian pediatric patients with Type 1 diabetes and in a control group. The diabetic condition is related positively to the positive electric charge of the pocket 4 of pro-inflammatory DRB1 alleles (R = 0.5072, P = 0.0001) and negatively to at least one anti-inflammatory RAGE allele (R = -0.2200, P = 0.0106). The association DRB1-disease decreases from high risk positively charged alleles to low risk negatively ones. A multiple regression model including the effect of electric charges at positions 70 and 74 of the DRB1 explains more than 31% of the variability of our data. The addition of the RAGE dependent variables does not increase the significance of the model. Our results confirm that the interaction between a negatively charged amino acid of insulin autoantigenic peptides and a positively charged DRB1 is the key event triggering the autoimmune process. The linkage disequilibrium between RAGE and DRB1 is the main cause of the association between the variants of RAGE and the initial outcome of the disease. However, since RAGE ligands increase during the disease progression, the observed association suggests that the proinflammatory RAGE and DRB1 polymorphisms synergize to activate the immune response which leads to the complications of diabetes. These evidences support a new hypothesis that considers the largely unexplored role of the MHC genes in genetic adaptation to a variable environment and in the maintenance of the metabolic biodiversity. A mechanism based on the maternal immunization against the negatively charged autoantigens, such as the insulin peptide B9-23, and on the fetal-maternal interaction might transform the physiological adaptation into adaptive changes of the genetic population structure. According to the \"thrifty-genotype\" hypothesis, \"thrifty DRB alleles\" with a positive charge are responsible for the susceptibility to diabetes and for an efficient storage of caloric intake in arctic climates with scarce food availability while \"non-thrifty DRB alleles\" with a negative or neutral charge are advantaged in tropical climates with constant food supply. (literal)

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