Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 d...

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Veröffentlicht in:Scientific reports Jg. 6; H. 1; S. 27887
Hauptverfasser: Törn, Carina, Liu, Xiang, Hagopian, William, Lernmark, Åke, Simell, Olli, Rewers, Marian, Ziegler, Anette-G, Schatz, Desmond, Akolkar, Beena, Onengut-Gumuscu, Suna, Chen, Wei-Min, Toppari, Jorma, Mykkänen, Juha, Ilonen, Jorma, Rich, Stephen S., She, Jin-Xiong, Sharma, Ashok, Steck, Andrea, Krischer, Jeffrey
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 16.06.2016
Nature Publishing Group
Schlagworte:
45
45/61
631/208/205
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Antigens
Autoantibodies
Autoimmune diseases
Basic Medicine
Child, Preschool
Clinical Medicine
Complement C3 - genetics
Complement C3 - immunology
Cytotoxicity
Diabetes
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - immunology
Endocrinology and Diabetes
Endokrinologi och diabetes
Enzymes
Female
Genes
Haplotypes
Health risk assessment
Humanities and Social Sciences
Humans
Immune system
Infant
Infant, Newborn
Insulin-Secreting Cells
Klinisk medicin
Lectins
Male
Medical and Health Sciences
Medical Genetics and Genomics (including Gene Therapy)
Medicin och hälsovetenskap
Medicinsk genetik och genomik (Här ingår: Genterapi)
Medicinska och farmaceutiska grundvetenskaper
multidisciplinary
Pathogens
Pediatrics
Polymorphism, Single Nucleotide
Proteins
Science
Science (multidisciplinary)
United States > US
Finland
ISSN:2045-2322, 2045-2322
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Zusammenfassung:A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54–91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66–0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65–0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01–1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05–2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43–0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75–5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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ISSN:2045-2322
2045-2322
DOI:10.1038/srep27887