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Törn, C.* ; Liu, X.* ; Hagopian, W.* ; Lernmark, A.* ; Simell, O.* ; Rewers, M.* ; Ziegler, A.-G. ; Schatz, D.* ; Akolkar, B.* ; Onengut-Gumuscu, S.* ; Chen, W.M.* ; Toppari, J.* ; Mykkänen, J.* ; Ilonen, J.* ; Rich, S.S.* ; She, J.X.* ; Sharma, A.* ; Steck, A.* ; Krischer, J.* ; TEDDY Study Group (Hummel, M. ; Hummel, S. ; Knopff, A. ; Peplow, C. ; Roth, R. ; Stock, J. ; Strauss, E. ; Warncke, K. ; Winkler, C.)

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

Sci. Rep. 6:27887 (2016)

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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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