caa a22 4500 467907455 CHVBK 20180406152838.0 cr unu---uuuuu 170328e20060601xx s 000 0 eng 10.1007/s00251-006-0088-3 doi (NATIONALLICENCE)springer-10.1007/s00251-006-0088-3 Association analysis of the AIRE and insulin genes in Finnish type 1 diabetic patients [Elektronische Daten] [Joni Turunen, Maija Wessman, Carol Forsblom, Riika Kilpikari, Maija Parkkonen, Nora Pöntynen, Tanja Ilmarinen, Ismo Ulmanen, Leena Peltonen, Per-Henrik Groop] Mutations in the autoimmune regulator (AIRE) gene cause a recessive Mendelian disorder autoimmune polyendocrinopathy syndrome type 1 (APS-1 or autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy). APS-1 patients develop multiorgan autoimmune diseases including type 1 diabetes (prevalence 12%). The AIRE protein controls the central tolerance induction in the thymus by regulating the expression levels of tissue-specific peripheral antigens, such as insulin. We hypothesized that the insulin gene (INS) polymorphisms together with the AIRE variations may predispose individuals to diabetes. The role of the AIRE gene was tested both independently and on the condition of the INS risk genotype in the Finnish type 1 diabetes sample. A total of 733 type 1 diabetic cases and 735 age- and sex-matched healthy controls were used in the analysis. Five common single nucleotide polymorphisms (SNPs) in the AIRE gene were selected from the public database (dbSNP). The −23HphI polymorphism was used as a surrogate marker for the INS gene promoter repeat. The five genotyped SNPs in the AIRE gene showed no evidence of association with type 1 diabetes. As expected, the INS gene polymorphism −23HphI was significantly associated with susceptibility to type 1 diabetes (P=6.8×10−12, χ2 test). When the subclass of patients carrying the homozygote genotype of the INS gene was used in the analysis, the AIRE polymorphisms showed no association with the disease. In conclusion, the AIRE gene does not seem to contribute to disease susceptibility in Finnish type 1 diabetic patients, whereas the insulin gene represents a notable risk factor for disease in this population. Springer-Verlag, 2006 Type 1 diabetes nationallicence AIRE nationallicence Insulin nationallicence Genetic predisposition to disease nationallicence Turunen Joni Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut Wessman Maija Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut Forsblom Carol Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut Kilpikari Riika Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut Parkkonen Maija Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut Pöntynen Nora Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland aut Ilmarinen Tanja Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland aut Ulmanen Ismo Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland aut Peltonen Leena Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland aut Groop Per-Henrik Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut Immunogenetics Springer-Verlag 58/5-6(2006-06-01), 331-338 0093-7711 58:5-6<331 2006 58 251 https://doi.org/10.1007/s00251-006-0088-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-006-0088-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Turunen Joni Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Wessman Maija Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Forsblom Carol Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Kilpikari Riika Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Parkkonen Maija Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut NATIONALLICENCE 700 1- Pöntynen Nora Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland aut NATIONALLICENCE 700 1- Ilmarinen Tanja Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland aut NATIONALLICENCE 700 1- Ulmanen Ismo Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland aut NATIONALLICENCE 700 1- Peltonen Leena Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland aut NATIONALLICENCE 700 1- Groop Per-Henrik Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Helsinki, Finland aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 58/5-6(2006-06-01), 331-338 0093-7711 58:5-6<331 2006 58 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer