PMID- 16683131
OWN - NLM
STAT- MEDLINE
DCOM- 20070419
LR  - 20211020
IS  - 0946-2716 (Print)
IS  - 0946-2716 (Linking)
VI  - 84
IP  - 7
DP  - 2006 Jul
TI  - Association of a polymorphism in the betacellulin gene with type 1 diabetes 
      mellitus in two populations.
PG  - 616-23
AB  - Betacellulin, a member of the epidermal growth factor family, is expressed in 
      fetal and adult pancreas. In vitro and in vivo studies suggest a role for 
      betacellulin in islet neogenesis and regeneration. Therefore, a mutation in the 
      betacellulin gene might lead to fewer beta cells. With reduced beta cell reserve, 
      beta cells may not be able to compensate for an autoimmune attack, and in turn, 
      susceptibility to type 1 diabetes mellitus (T1DM) would increase. Previous 
      mutational analysis identified seven polymorphisms in the betacellulin gene [5' 
      UT (-233G>C, -226A>G), exon 1 (TGC19GGC, Cys7Gly), exon 2 (CTC130TTC, Leu44Phe), 
      exon 4 (TTG370ATG, Leu124Met), intron 2 (-31T>C), and intron 4 (-4C>T)]. An 
      association study of these variants with T1DM was first carried out in 100 
      Caucasian subjects with T1DM and 282 Caucasian subjects without diabetes 
      recruited at the University of Maryland. The frequency of the intron 4 T-4 allele 
      was significantly higher among nondiabetic controls than that among diabetic 
      cases (0.29 vs 0.21, p=0.04). Allele frequencies for the other polymorphisms did 
      not differ significantly between cases and controls. The intron 4 T-4 association 
      was then replicated by transmission disequilibrium testing in a separate 
      population of Caucasian parent/offspring with T1DM trios (n=168 trios, 113 
      informative) recruited at the Medical College of Wisconsin (p=0.024). An 
      interaction of the intron 4 T-4 allele and human leukocyte antigen (HLA) was also 
      detected with undertransmission of the T allele in those T1DM subjects with 
      susceptible HLA types as compared to those T1DM subjects without susceptible HLA 
      types (p=0.018). RNA studies of the intron T-4 variant showed similar RNA levels 
      for intron 4 T-4 and intron 4 C-4 alleles. Additionally, there was no evidence 
      for an effect of this variant on exon-intron splicing. We conclude that the 
      intron 4 T-4 allele in the betacellulin gene is associated with lower risk of 
      T1DM and may interact with HLA. Further studies will be necessary to establish 
      the significance of this association.
FAU - Silver, Kristi D
AU  - Silver KD
AD  - Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, 
      University of Maryland School of Medicine, Baltimore, 21201, USA. 
      ksilver@medicine.umaryland.edu
FAU - Magnuson, Victoria L
AU  - Magnuson VL
FAU - Tolea, Magdalena
AU  - Tolea M
FAU - Wang, Jian
AU  - Wang J
FAU - Hagopian, William A
AU  - Hagopian WA
FAU - Mitchell, Braxton D
AU  - Mitchell BD
LA  - eng
GR  - 1K23DK02945-01/DK/NIDDK NIH HHS/United States
GR  - 1R03DK062923-01/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060509
PL  - Germany
TA  - J Mol Med (Berl)
JT  - Journal of molecular medicine (Berlin, Germany)
JID - 9504370
RN  - 0 (BTC protein, human)
RN  - 0 (Betacellulin)
RN  - 0 (HLA Antigens)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 5CSZ8459RP (Cytidine)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Betacellulin
MH  - Cytidine/genetics
MH  - Diabetes Mellitus, Type 1/epidemiology/*genetics
MH  - Female
MH  - HLA Antigens/genetics
MH  - Haplotypes/genetics
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Introns/genetics
MH  - Male
MH  - Polymorphism, Genetic/*genetics
EDAT- 2006/05/10 09:00
MHDA- 2007/04/20 09:00
CRDT- 2006/05/10 09:00
PHST- 2005/05/11 00:00 [received]
PHST- 2006/02/22 00:00 [accepted]
PHST- 2006/05/10 09:00 [pubmed]
PHST- 2007/04/20 09:00 [medline]
PHST- 2006/05/10 09:00 [entrez]
AID - 10.1007/s00109-006-0052-6 [doi]
PST - ppublish
SO  - J Mol Med (Berl). 2006 Jul;84(7):616-23. doi: 10.1007/s00109-006-0052-6. Epub 
      2006 May 9.