PMID- 10199786
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20061115
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 4
DP  - 1999 Apr
TI  - The presence or absence of a retroviral long terminal repeat influences the 
      genetic risk for type 1 diabetes conferred by human leukocyte antigen DQ 
      haplotypes. Belgian Diabetes Registry.
PG  - 1404-8
AB  - Major genetic susceptibility to type 1 diabetes mellitus maps to the human 
      leukocyte antigen (HLA) region on chromosome 6p. During evolution, endogenous 
      retroviral long terminal repeats (LTR) have been integrated at several sites 
      within this region. We analyzed the presence of a solitary HERV-K LTR in the HLA 
      DQ region (DQ-LTR3) and its linkage to DRB1, DQA1, and DQB1 haplotypes derived 
      from 246 German and Belgian families with a patient suffering from type 1 
      diabetes mellitus. Segregation analysis of 984 HLA DQA1/B1 haplotypes showed that 
      DQ-LTR3 is linked to distinct DQA1 and DQB1 haplotypes but is absent in others. 
      The presence of DQ-LTR3 on HLA DQB1*0302 haplotypes was preferentially 
      transmitted to patients from heterozygous parents (82%; P < 10(-6)), in contrast 
      to only 2 of 7 DQB1*0302 haplotypes without DQ-LTR3. Also, the extended HLA 
      DRB1*0401, DQB1*0302 DQ-LTR3-positive haplotypes were preferentially transmitted 
      (84%; P < 10(-6)) compared with 1 of 6 DR-DQ matched DQ-LTR3 negative haplotypes. 
      DQ-LTR3 is missing on most DQB1*0201 haplotypes, and those LTR3 negative 
      haplotypes were also preferentially transmitted to patients (80%; P < 10(-6)), 
      whereas DQB1*0201 DQ-LTR3-positive haplotypes were less often transmitted to 
      patients (36%). Other DQA1/B1 haplotypes did not differ for DQ-LTR3 between 
      transmitted and nontransmitted haplotypes. Thus, the presence of DQLTR3 on HLA 
      DQB1*0302 and its absence on DQB1*0201 haplotypes are independent genetic risk 
      markers for type 1 diabetes.
FAU - Donner, H
AU  - Donner H
AD  - Center of Internal Medicine, Medical Department I, University Hospital, Frankfurt 
      am Main, Germany.
FAU - Tonjes, R R
AU  - Tonjes RR
FAU - Van der Auwera, B
AU  - Van der Auwera B
FAU - Siegmund, T
AU  - Siegmund T
FAU - Braun, J
AU  - Braun J
FAU - Weets, I
AU  - Weets I
FAU - Herwig, J
AU  - Herwig J
FAU - Kurth, R
AU  - Kurth R
FAU - Usadel, K H
AU  - Usadel KH
FAU - Badenhoop, K
AU  - Badenhoop K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (HLA-DQ Antigens)
SB  - IM
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Endogenous Retroviruses/*genetics
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - HLA-DQ Antigens/*genetics
MH  - *Haplotypes
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - *Terminal Repeat Sequences
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
AID - 10.1210/jcem.84.4.5638 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Apr;84(4):1404-8. doi: 10.1210/jcem.84.4.5638.