PMID- 22151770
OWN - NLM
STAT- MEDLINE
DCOM- 20121221
LR  - 20221207
IS  - 1399-5448 (Electronic)
IS  - 1399-543X (Print)
IS  - 1399-543X (Linking)
VI  - 13
IP  - 5
DP  - 2012 Aug
TI  - Gene CNVs and protein levels of complement C4A and C4B as novel biomarkers for 
      partial disease remissions in new-onset type 1 diabetes patients.
PG  - 408-18
LID - 10.1111/j.1399-5448.2011.00836.x [doi]
AB  - OBJECTIVE: To 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 beta-cell function in new-onset type 1 diabetes (T1D) 
      patients. METHODS: 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. RESULTS: 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). 
      CONCLUSIONS: C4A appears to associate with the protection of residual beta-cell 
      function in new-onset T1D; C4B is correlated with the end of disease remission at 
      9-month post diagnosis.
CI  - (c) 2011 John Wiley & Sons A/S.
FAU - Kingery, Suzanne E
AU  - Kingery SE
AD  - Center for Molecular and Human Genetics, The Research Institute at Nationwide 
      Children's Hospital, Columbus, OH 43205, USA.
FAU - Wu, Yee Ling
AU  - Wu YL
FAU - Zhou, Bi
AU  - Zhou B
FAU - Hoffman, Robert P
AU  - Hoffman RP
FAU - Yu, C Yung
AU  - Yu CY
LA  - eng
GR  - R01 AR054459/AR/NIAMS NIH HHS/United States
GR  - UL1 RR025755/RR/NCRR NIH HHS/United States
GR  - HD051997/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111213
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
RN  - 0 (Biomarkers)
RN  - 0 (C-Peptide)
RN  - 0 (HLA-DR3 Antigen)
RN  - 80295-49-4 (Complement C4a)
RN  - 80295-50-7 (Complement C4b)
SB  - IM
MH  - Adolescent
MH  - Biomarkers
MH  - C-Peptide/genetics
MH  - Child
MH  - Child, Preschool
MH  - Complement C4a/*genetics
MH  - Complement C4b/*genetics
MH  - DNA Copy Number Variations
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Female
MH  - *Gene Dosage
MH  - HLA-DR3 Antigen/genetics
MH  - Humans
MH  - Insulin-Secreting Cells/*physiology
MH  - Male
MH  - Recovery of Function
MH  - White People/genetics
PMC - PMC4178531
MID - NIHMS333882
EDAT- 2011/12/14 06:00
MHDA- 2012/12/22 06:00
PMCR- 2014/09/29
CRDT- 2011/12/14 06:00
PHST- 2011/06/21 00:00 [received]
PHST- 2011/10/17 00:00 [accepted]
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/12/22 06:00 [medline]
PHST- 2014/09/29 00:00 [pmc-release]
AID - 10.1111/j.1399-5448.2011.00836.x [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2012 Aug;13(5):408-18. doi: 10.1111/j.1399-5448.2011.00836.x. 
      Epub 2011 Dec 13.