PMID- 15245369
OWN - NLM
STAT- MEDLINE
DCOM- 20050128
LR  - 20111117
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 64
IP  - 2
DP  - 2004 Aug
TI  - Molecular basis of predisposition to develop type 1 diabetes mellitus in North 
      Indians.
PG  - 145-55
AB  - Type 1 diabetes (T1D) mellitus is a multifactorial autoimmune disease where more 
      than 90% of insulin-producing pancreatic beta cells are destroyed before the 
      clinical manifestations, warranting a need to identify the children predisposed 
      to get the disease. Of the 20 genomic intervals implicated for the risk to 
      develop T1D, the major histocompatibility complex (MHC) region on chromosome 
      6p21.31 (IDDM1) has been the major contributor, followed by 5' regulatory region 
      of the insulin (INS) gene on chromosome 11p15.5 (IDDM2). MHC has a role in 
      antigen presentation and IDDM2 has been shown to have a role in transcription of 
      insulin in the thymus. Hence, alleles of human leukocyte antigen (HLA)-DRB1, 
      DQB1, and insulin-linked variable number of tandem repeats (INS-VNTR) were 
      studied in 110 T1D patients and 112 healthy controls using polymerase chain 
      reaction and hybridization with sequence-specific oligonucleotide probes 
      (PCR-SSOP) and PCR restriction fragment length polymorphism (PCR-RFLP), 
      respectively. HLA-DRB1*0301 was significantly increased in the T1D patients along 
      with associated DQB1*0201 followed by DRB1*0401 and DRB1*0405. DRB1*0701 was 
      observed to be the most protective allele followed by DRB1*0403 and DRB1*0404. 
      Although DQB1*0302 which is associated with both the protective and susceptible 
      DR4 alleles was not significantly increased, heterozygous DQB1*0201, *0302 was 
      significantly increased in the TID patients. Because INS-VNTR class I 
      homozygosity was also significantly increased in the patients, simultaneous 
      presence of DRB1*0301 along with homozygous INS-VNTR class I, gave a relative 
      risk (RR) of 70.81. However, a similar analysis of DQB1*0201 and *0302 along with 
      INS-VNTR alleles did not give such high RRs. Thus, the two independently 
      assorting alleles at two loci i.e., DRB1*0301 and INS-VNTR class I, on two 
      different chromosomes may have the potential to predict a prediabetic in North 
      India.
FAU - Rani, R
AU  - Rani R
AD  - Neuroimmunology Laboratory, National Institute of Immunology, Aruna Asafali Marg, 
      New Delhi, India. rajni@nii.res.in
FAU - Sood, A
AU  - Sood A
FAU - Goswami, R
AU  - Goswami R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
RN  - 0 (HLA-DRB1*04:01 antigen)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - India
MH  - Male
EDAT- 2004/07/13 05:00
MHDA- 2005/01/29 09:00
CRDT- 2004/07/13 05:00
PHST- 2004/07/13 05:00 [pubmed]
PHST- 2005/01/29 09:00 [medline]
PHST- 2004/07/13 05:00 [entrez]
AID - TAN246 [pii]
AID - 10.1111/j.1399-0039.2004.00246.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2004 Aug;64(2):145-55. doi: 10.1111/j.1399-0039.2004.00246.x.