PMID- 17174749
OWN - NLM
STAT- MEDLINE
DCOM- 20070202
LR  - 20181113
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 67
IP  - 12
DP  - 2006 Dec
TI  - Linkage disequilibrium with predisposing DR3 haplotypes accounts for apparent 
      effects of tumor necrosis factor and lymphotoxin-alpha polymorphisms on type 1 
      diabetes susceptibility.
PG  - 999-1004
AB  - Tumor necrosis factor (TNF) and lymphotoxin alpha (LT-alpha) are immunomodulators 
      that have been hypothesized to contribute to susceptibility to type 1 diabetes 
      (T1D). Several polymorphisms in the TNF and LT-alpha loci have been extensively 
      studied for T1D association, with conflicting reports. In this study, we examined 
      two TNF variants and one LT-alpha variant for T1D association in 283 Caucasian, 
      multiplex T1D families for which complete human leukocyte antigen (HLA) 
      genotyping data are available. Initially, association with T1D was seen for 
      LT-alpha A1069G (intron A, p=0.011, rs909253) and TNF G(-308)A (p<1x10(-5), 
      rs1800629), but no association was observed for TNF G(-238)A (rs361525). After 
      adjusting the data for linkage disequilibrium (LD) with DRB1-DQB1 haplotypes, 
      however, only one polymorphism, TNF G(-238)A showed significant association with 
      T1D (p<0.006). When HLA-DR3 haplotypes were examined, the A allele of TNF 
      G(-238)A was significantly overtransmitted to affected offspring (p<0.009). 
      Including HLA-B data in the analysis revealed that TNF (-238)A is present 
      exclusively on DR3 haplotypes that also carry HLA-B18. Transmission proportion of 
      B18-DR3 haplotypes did not differ between those with TNF (-238)A and those with 
      TNF (-238)G. Thus, variation at TNF does not affect the T1D risk for B18-DR3 
      haplotypes, and the apparent association of TNF(-238)A with T1D may simply 
      reflect its presence on a high-risk haplotype.
FAU - Noble, Janelle A
AU  - Noble JA
AD  - Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. 
      jnoble@chori.org
FAU - Valdes, Ana M
AU  - Valdes AM
FAU - Lane, Julie A
AU  - Lane JA
FAU - Green, Amy E
AU  - Green AE
FAU - Erlich, Henry A
AU  - Erlich HA
LA  - eng
GR  - R01 DK061722/DK/NIDDK NIH HHS/United States
GR  - R56 DK061722/DK/NIDDK NIH HHS/United States
GR  - DK61722/DK/NIDDK NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061030
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Lymphotoxin-alpha)
RN  - 0 (Receptors, Tumor Necrosis Factor, Member 25)
RN  - 0 (TNFRSF25 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Haplotypes
MH  - Humans
MH  - *Linkage Disequilibrium
MH  - Lymphotoxin-alpha/*genetics/immunology
MH  - Male
MH  - *Polymorphism, Single Nucleotide
MH  - Receptors, Tumor Necrosis Factor, Member 25/*genetics/immunology
MH  - Tumor Necrosis Factor-alpha/*genetics/immunology
PMC - PMC2481238
MID - NIHMS15616
EDAT- 2006/12/19 09:00
MHDA- 2007/02/03 09:00
PMCR- 2008/07/22
CRDT- 2006/12/19 09:00
PHST- 2006/07/28 00:00 [received]
PHST- 2006/09/19 00:00 [revised]
PHST- 2006/10/02 00:00 [accepted]
PHST- 2006/12/19 09:00 [pubmed]
PHST- 2007/02/03 09:00 [medline]
PHST- 2006/12/19 09:00 [entrez]
PHST- 2008/07/22 00:00 [pmc-release]
AID - S0198-8859(06)00550-7 [pii]
AID - 10.1016/j.humimm.2006.10.002 [doi]
PST - ppublish
SO  - Hum Immunol. 2006 Dec;67(12):999-1004. doi: 10.1016/j.humimm.2006.10.002. Epub 
      2006 Oct 30.