Suzanne E Kingery, Yee Ling Wu, Bi Zhou, Robert P Hoffman, C Yung Yu
Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Pediatric diabetes 2012 AugTo determine the roles of complement C4A and C4B gene copy-number variations and their plasma protein concentrations in residual insulin secretion and loss of pancreatic β-cell function in new-onset type 1 diabetes (T1D) patients. We studied 34 patients of European ancestry with new-onset T1D, aged between 3 and 17 yr (10.7 ± 3.45), at Nationwide Children's Hospital in Columbus, Ohio. Gene copy-number and size variations of complement C4A and C4B were determined by genomic Southern blot analyses. C4A and C4B protein phenotypes were elucidated by immunofixation and radial immunodiffusion. Two-digit human leukocyte antigen (HLA)-DRB1 genotypes were determined by sequence-specific polymerase chain reaction. At 1- and 9-month post diagnosis, stimulated C-peptide levels were measured after a standardized mixed-meal tolerance test. The diploid gene copy-numbers of C4A varied from 0 to 4, and those of C4B from 0 to 3. Patients with higher copy-number of C4A or higher C4A plasma protein concentrations at diagnosis had higher C-peptide levels at 1-month post diagnosis (p = 0.008; p = 0.008). When controlled by the Z-score of body mass index, C4A copy-numbers, C4A protein concentrations, the age of disease onset, and the number of HLA-DR3 but not DR4 alleles were significant parameters in determining C-peptide levels. At 9-month post diagnosis, 42.3% of patients remained in partial remission, and these patients were characterized by lower total C4B copy-numbers or lower C4B protein concentrations (p = 0.02; p = 0.0004). C4A appears to associate with the protection of residual β-cell function in new-onset T1D; C4B is correlated with the end of disease remission at 9-month post diagnosis. © 2011 John Wiley & Sons A/S.
Suzanne E Kingery, Yee Ling Wu, Bi Zhou, Robert P Hoffman, C Yung Yu. Gene CNVs and protein levels of complement C4A and C4B as novel biomarkers for partial disease remissions in new-onset type 1 diabetes patients. Pediatric diabetes. 2012 Aug;13(5):408-18
PMID: 22151770
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