PMID- 1442714
OWN - NLM
STAT- MEDLINE
DCOM- 19921214
LR  - 20190509
IS  - 0002-9262 (Print)
IS  - 0002-9262 (Linking)
VI  - 136
IP  - 5
DP  - 1992 Sep 1
TI  - Autoimmunity and genetics contribute to the risk of insulin-dependent diabetes 
      mellitus in families: islet cell antibodies and HLA DQ heterodimers.
PG  - 503-12
AB  - The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic 
      susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci 
      was evaluated among individuals with and those without islet cell antibodies. A 
      total of 108 antibody-positive parents and siblings of IDDM patients from the 
      Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ 
      molecular typing was performed on 79 of these individuals and on 78 
      antibody-negative relatives. There were similar proportions of homozygotes for 
      both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 
      (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 
      15.4%, respectively). However, subsequent development of IDDM was restricted to 
      individuals who were both antibody positive and carried the potential to make at 
      least one diabetogenic DQ heterodimer. A dose-response effect was observed among 
      the antibody-positive relatives, in which two of 18 capable of generating one 
      diabetogenic heterodimer and six of 29 generating two heterodimers became insulin 
      requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding 
      exclusively for diabetogenic variants, became diabetic over the course of the 
      follow-up. With a multivariate model, the relative risk for IDDM among those with 
      islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 
      compared with those lacking both, after age and sex were controlled for. The data 
      suggest that while autoimmunity, indicated by the presence of cytoplasmic islet 
      cell antibodies may be relatively common, it progresses only in those with 
      variant HLA-DQ molecules.
FAU - Lipton, R B
AU  - Lipton RB
AD  - Department of Epidemiology, Graduate School of Public Health, University of 
      Pittsburgh, PA.
FAU - Kocova, M
AU  - Kocova M
FAU - LaPorte, R E
AU  - LaPorte RE
FAU - Dorman, J S
AU  - Dorman JS
FAU - Orchard, T J
AU  - Orchard TJ
FAU - Riley, W J
AU  - Riley WJ
FAU - Drash, A L
AU  - Drash AL
FAU - Becker, D J
AU  - Becker DJ
FAU - Trucco, M
AU  - Trucco M
LA  - eng
GR  - DK 2402/DK/NIDDK NIH HHS/United States
GR  - GCRC 5MO1RR00084/RR/NCRR NIH HHS/United States
GR  - HD 19469/HD/NICHD NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Epidemiol
JT  - American journal of epidemiology
JID - 7910653
RN  - 0 (Antibodies)
RN  - 0 (Genetic Markers)
RN  - 0 (HLA-DQ Antigens)
SB  - IM
CIN - Am J Epidemiol. 1993 Nov 15;138(10):905-8. PMID: 8237977
MH  - Adolescent
MH  - Adult
MH  - Antibodies/*blood
MH  - Autoimmune Diseases/*epidemiology/genetics/immunology
MH  - Diabetes Mellitus, Type 1/*epidemiology/genetics/immunology
MH  - Female
MH  - Genetic Markers/*genetics
MH  - Genetic Testing/standards
MH  - HLA-DQ Antigens/*immunology
MH  - Histocompatibility Testing/standards
MH  - Humans
MH  - Islets of Langerhans/*immunology
MH  - Male
MH  - Middle Aged
MH  - Models, Genetic
MH  - Multivariate Analysis
MH  - Pennsylvania/epidemiology
MH  - Predictive Value of Tests
MH  - Registries
MH  - Risk Factors
EDAT- 1992/09/01 00:00
MHDA- 1992/09/01 00:01
CRDT- 1992/09/01 00:00
PHST- 1992/09/01 00:00 [pubmed]
PHST- 1992/09/01 00:01 [medline]
PHST- 1992/09/01 00:00 [entrez]
AID - 10.1093/oxfordjournals.aje.a116528 [doi]
PST - ppublish
SO  - Am J Epidemiol. 1992 Sep 1;136(5):503-12. doi: 
      10.1093/oxfordjournals.aje.a116528.