Variations of the Perforin Gene in Patients With Type 1 Diabetes
| العنوان: | Variations of the Perforin Gene in Patients With Type 1 Diabetes |
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| المؤلفون: | Giuseppe d'Annunzio, Giuseppe Cappellano, Massimo Ferretti, Francesco Cadario, Elisabetta Orilieri, Miryam Martinetti, Elisa Cerutti, Graziella Bruno, Angela Cometa, Umberto Dianzani, Franco Cerutti, Rita Clementi, Valeria Calcaterra, Annalisa Chiocchetti, Daniela Larizza, Renata Lorini |
| المصدر: | Diabetes. 57:1078-1083 |
| بيانات النشر: | American Diabetes Association, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Adult, Male, Pore Forming Cytotoxic Proteins, Adolescent, Endocrinology, Diabetes and Metabolism, Population, Biology, Polymorphism, Single Nucleotide, HLA-DQ alpha-Chains, Cohort Studies, Gene Frequency, Reference Values, Polymorphism (computer science), HLA-DQ Antigens, Internal Medicine, medicine, HLA-DQ beta-Chains, Humans, Genetic Predisposition to Disease, Allele, education, Allele frequency, DNA Primers, Type 1 diabetes, education.field_of_study, Perforin, Genetic Variation, Odds ratio, Familial Hemophagocytic Lymphohistiocytosis, medicine.disease, Diabetes Mellitus, Type 1, Amino Acid Substitution, Italy, Immunology, biology.protein, Female |
| الوصف: | OBJECTIVE—Perforin plays a key role in cell-mediated cytotoxicity. Mutations of its gene, PRF1, cause familial hemophagocytic lymphohistiocytosis but have also been associated with lymphomas and the autoimmune/lymphoproliferative syndrome. The aim of this work was to investigate the role of PRF1 variations in type 1 diabetes. RESEARCH DESIGN AND METHODS—We typed for the N252S and A91V variations in an initial population of 352 type 1 diabetic patients and 816 control subjects and a second population of 365 patients and 964 control subjects. Moreover, we sequenced the coding sequence and intron-exons boundaries in 200 patients and 300 control subjects. RESULTS—In both cohorts, allelic frequency of N252S was significantly higher in patients than in control subjects (combined cohorts: 1.5 vs. 0.4%; odds ratio 6.68 [95% CI 1.83–7.48]). Sequencing of the entire coding region detected one novel mutation in one patient, causing a P477A amino acid change not detected in 199 patients and 300 control subjects. Typing for HLA-DQA1 and DQB1 alleles showed that type 1 diabetes–predisposing DQα/DQβ heterodimers were less frequent in patients carrying N252S or P477A than in those carrying wild-type PRF1. We previously found that natural killer (NK) activity is not decreased in most N252S heterozygotes, but we detected one whose NK activity was normal at the age of 12 but strikingly low in early childhood. Here, we discovered that NK function was low in three heterozygotes in early childhood, one homozygous adult, and in the subject carrying P477A. CONCLUSIONS—These data suggest that N252S and possibly other PRF1 variations are susceptibility factors for type 1 diabetes development. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::31afb8328a9b8c9ff629c26b2585fc0aTest https://doi.org/10.2337/db07-0947Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....31afb8328a9b8c9ff629c26b2585fc0a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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