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

Törn, Carina LU ; Liu, Xiang; Hagopian, William; Lernmark, Åke LU ; Simell, Olli; Rewers, Marian; Ziegler, Anette G.; Schatz, Desmond; Akolkar, Beena and Onengut-Gumuscu, Suna, et al. (2016) In Scientific Reports 6.
Abstract

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 =... (More)

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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Scientific Reports
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6
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Nature Publishing Group
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  • scopus:84975091581
  • wos:000378028900001
ISSN
2045-2322
DOI
10.1038/srep27887
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English
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2017-01-23 09:43:32
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@article{a6bd2eda-f624-4dc4-b346-a05436236e9f,
  abstract     = {<p>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 &lt; 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.</p>},
  articleno    = {27887},
  author       = {Törn, Carina and Liu, Xiang and Hagopian, William and Lernmark, Åke and Simell, Olli and Rewers, Marian and Ziegler, Anette G. and Schatz, Desmond and Akolkar, Beena and Onengut-Gumuscu, Suna and Chen, Wei Min and Toppari, Jorma and Mykkänen, Juha and Ilonen, Jorma and Rich, Stephen S. and She, Jin Xiong and Sharma, Ashok and Steck, Andrea and Krischer, Jeffrey and Agardh, Daniel and Andrén Aronsson, Carin and Ask, Maria and Bennet, Rasmus and Bremer, Jenny and Carlsson, Ulla-Marie and Cilio, Corrado and Larsson, Helena and Ericson-Hallström, Emelie and Fransson, Lina and Gard, Thomas and Gerardsson, Joanna and Hansen, Monica and Hansson, Gertie and Harmby, Cecilia and Hyberg-Karlsson, Suzanne and Johansen, Fredrik and Jonsdottir, Berglind and Lenrick Forss, Sigrid and Lundgren, Markus and Markan, Maria and Melin, Marie Jessica and Mestan, Zeliha and Månsson Martinez, Maria and Rahmati, Kobra and Ramelius, Anita and Rosenquist, Anna and Salami, Falastin and Sibthorpe, Sara and Sjöberg, Birgitta and Swartling, Ulrica and Amboh, Evelyn Tekum and Wallin, Anne and Wimar, Åsa and Åberg, Sofie},
  issn         = {2045-2322},
  language     = {eng},
  month        = {06},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study},
  url          = {http://dx.doi.org/10.1038/srep27887},
  volume       = {6},
  year         = {2016},
}