PMID- 22366579
OWN - NLM
STAT- MEDLINE
DCOM- 20130118
LR  - 20120427
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 73
IP  - 5
DP  - 2012 May
TI  - Tumor necrosis factor-associated susceptibility to type 1 diabetes is caused by 
      linkage disequilibrium with HLA-DR3 haplotypes.
PG  - 566-73
LID - 10.1016/j.humimm.2012.01.012 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important proinflammatory cytokine involved 
      in the pathogenesis of autoimmune type 1 diabetes (T1D). The TNF gene locus is 
      located in the major histocompatibility complex (MHC) class III region and its 
      genetic polymorphisms have been reported to be associated with T1D. However, it 
      is not clear whether these associations are primary or caused by their linkage 
      disequilibrium with other predisposing genes within the MHC. We have tested 2 
      TNF-alpha single nucleotide polymorphisms at positions -308G/A and -238G/A in the 5' 
      untranslated region and a (GT)n microsatellite TNFa in the North Indian healthy 
      population and T1D patients with known HLA-A-B-DR-DQ haplotypes. The allele 
      frequencies of TNFa5, -308A, and -238G were determined to be significantly 
      increased among patients compared with controls. Although the observed positive 
      association of -238G was caused by its presence on all 3 DR3(+) groups, namely, 
      B8-DR3-DQ2, B50-DR3-DQ2, and B58-DR3-DQ2 haplotypes associated with T1D in this 
      population, the increase of the -308A allele was caused by its association with 
      the latter 2 haplotypes. On the other hand, TNF -308G occurred on B8-DR3 
      haplotypes along with -238G and TNFa5 alleles, particularly in T1D patients with 
      late disease onset (at >20 years of age). These results indicate that TNF 
      associations with T1D are caused by their linkage disequilibrium with specific 
      HLA-DR3-DQ2 haplotypes in the Indian population. Because polymorphisms in the 
      promoter region regulate TNF expression levels (e.g., -308A), they retain crucial 
      immunological significance in the development of T1D and its management.
CI  - Copyright (c) 2012 American Society for Histocompatibility and Immunogenetics. 
      Published by Elsevier Inc. All rights reserved.
FAU - Kumar, Neeraj
AU  - Kumar N
AD  - Department of Transplant Immunology and Immunogenetics, All India Institute of 
      Medical Sciences, New Delhi, India.
FAU - Kaur, Gurvinder
AU  - Kaur G
FAU - Tandon, Nikhil
AU  - Tandon N
FAU - Mehra, Narinder
AU  - Mehra N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120209
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (5' Untranslated Regions)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Adolescent
MH  - Adult
MH  - Age of Onset
MH  - Alleles
MH  - Case-Control Studies
MH  - Child
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Female
MH  - Gene Frequency
MH  - Genetic Loci
MH  - Genetic Predisposition to Disease
MH  - HLA-DR3 Antigen/*genetics/immunology
MH  - Haplotypes
MH  - Humans
MH  - *Linkage Disequilibrium
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Tumor Necrosis Factor-alpha/*genetics/immunology
EDAT- 2012/03/01 06:00
MHDA- 2013/01/19 06:00
CRDT- 2012/02/28 06:00
PHST- 2011/11/25 00:00 [received]
PHST- 2012/01/13 00:00 [revised]
PHST- 2012/01/24 00:00 [accepted]
PHST- 2012/02/28 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2013/01/19 06:00 [medline]
AID - S0198-8859(12)00022-5 [pii]
AID - 10.1016/j.humimm.2012.01.012 [doi]
PST - ppublish
SO  - Hum Immunol. 2012 May;73(5):566-73. doi: 10.1016/j.humimm.2012.01.012. Epub 2012 
      Feb 9.