PMID- 11345587
OWN - NLM
STAT- MEDLINE
DCOM- 20010531
LR  - 20190901
IS  - 0093-7711 (Print)
IS  - 0093-7711 (Linking)
VI  - 53
IP  - 2
DP  - 2001 Mar
TI  - Distribution of HERV-LTR elements in the 5'-flanking region of HLA-DQB1 and 
      association with autoimmunity.
PG  - 114-8
AB  - We established the detailed polymorphism of the 5'-flanking region and the first 
      exon of the human leukocyte antigen (HLA)-DQB1 alleles. One hundred and 
      forty-five Spanish rheumatoid arthritis (RA) patients and 200 healthy voluntary 
      blood donors from southern Spain along with 42 B-cell lines were analyzed for the 
      presence of the retrovirus-derived long terminal repeats (LTRs) LTR3, LTR5, and 
      LTR13. LTR3 positivity was always associated with certain DQB1 alleles, i.e., 
      *0302, *0402, *0601, *0202, and *0305. Sequencing analysis of the 5'-flanking 
      region of DQB1*0301, *0303 and *0502 alleles in homozygous B-cell lines showed 
      the absence of LTR3 and a massive deletion of 5635 base pairs. The undetected 
      deletion in the flanking region of some DQB1 alleles and a lack of stratification 
      for HLA typing explain previously reported associations of the LTR3 element with 
      RA and type I diabetes (IDDM). LTR5 showed identical distribution to LTR3, 
      consistent with a previously suggested LTR3-LTR5 tandem arrangement. LTR13 
      positivity was associated with DQB1*0302, *0303, and *0402 alleles. Distributions 
      of the LTR elements in all B-cell lines, RA patients, and controls could be 
      explained entirely by linkage disequilibrium with DQB1 alleles, independently of 
      the haplotypes carrying them. LTR elements are known to regulate gene expression. 
      Therefore, a possible involvement of LTR13 in the association of DQB1*0302, 
      *0303, and *0402 with IDDM requires further investigation. The sequencing results 
      of the DQB1 first exon demonstrated that DQB1*0601 was generated by a 
      recombination event between a DR53 and a non-DR53 haplotype. Our results shed new 
      light on the phylogeny of the HLA region and the possible contribution of DQB1 to 
      susceptibility to autoimmunity.
FAU - Pascual, M
AU  - Pascual M
AD  - Instituto de Parasitologia y Biomedicina Lopez Neyra, CSIC, C/Ventanilla no 11, 
      18001 Granada, Spain. martin@ipb.csic.es
FAU - Martin, J
AU  - Martin J
FAU - Nieto, A
AU  - Nieto A
FAU - Giphart, M J
AU  - Giphart MJ
FAU - van der Slik, A R
AU  - van der Slik AR
FAU - de Vries, R R
AU  - de Vries RR
FAU - Zanelli, E
AU  - Zanelli E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (DNA Primers)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Alleles
MH  - Arthritis, Rheumatoid/genetics/immunology
MH  - Autoimmunity/*genetics
MH  - B-Lymphocytes/immunology
MH  - Base Sequence
MH  - Case-Control Studies
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - Diabetes Mellitus, Type 1/genetics/immunology
MH  - Endogenous Retroviruses/*genetics
MH  - Exons
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ beta-Chains
MH  - Humans
MH  - Polymorphism, Genetic
MH  - Spain
MH  - *Terminal Repeat Sequences
EDAT- 2001/05/11 10:00
MHDA- 2001/06/02 10:01
CRDT- 2001/05/11 10:00
PHST- 2001/05/11 10:00 [pubmed]
PHST- 2001/06/02 10:01 [medline]
PHST- 2001/05/11 10:00 [entrez]
AID - 10.1007/s002510100307 [doi]
PST - ppublish
SO  - Immunogenetics. 2001 Mar;53(2):114-8. doi: 10.1007/s002510100307.