PMID- 7813806
OWN - NLM
STAT- MEDLINE
DCOM- 19950207
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 44
IP  - 1
DP  - 1995 Jan
TI  - Polymorphic amino acid variations in HLA-DQ are associated with systematic 
      physical property changes and occurrence of IDDM. Members of the Swedish 
      Childhood Diabetes Study.
PG  - 125-31
AB  - The association between human leukocyte antigen (HLA) and insulin-dependent 
      diabetes was studied in a large population-based investigation using genotyping 
      of 425 new-onset patients, 0-14 years of age, and 367 matched control subjects. 
      As many as 97% of patients compared with 75% of control subjects were positive 
      for one or several of DQA1*0301, DQA1*0501, DQB1*0302, or DQB1*0201. Asp-57 DQB 
      was present among 28% of patients, indicating that this residue alone does not 
      confer protection. Combining Asp-57 DQB1 with either Arg-52 DQA1 or Leu-69 DQA1 
      did not explain susceptibility or protection either. DQA1*0301-DQB1*0302 (DQ8) 
      and DQA1*0301-DQB1*0301 (DQ7) are identical except for four amino acid 
      substitutions in the beta-chain, but DQ8 was positively (odds ratio 8.07; P < 
      0.001) and DQ7 negatively (odds ratio 0.38; P < 0.001) associated with the 
      disease. Molecular modeling was used to determine whether physiochemical 
      properties such as steric factors and surface electrostatic potentials also 
      differ in a systematic way for various DQ molecules. Amino acids were substituted 
      systematically at the four polymorphic sites, and the solvent-accessible surfaces 
      and electrostatic potentials were computed for each molecule. Dramatic 
      alterations in electrostatic potential were seen for double substitutions at 
      position 45 (G45E) and 57 (A57D) of DQB1. The variation of physicochemical 
      properties due to polymorphic substitutions may be significant to the mechanism 
      of HLA-DQ association with insulin-dependent diabetes, via the effect these 
      property variations have on peptide antigen binding selectivity and subsequent 
      interactions with specific T-cell receptors.
FAU - Sanjeevi, C B
AU  - Sanjeevi CB
AD  - Karolinska Institute, Department of Molecular Medicine, Karolinska Hospital, 
      Stockholm, Sweden.
FAU - Lybrand, T P
AU  - Lybrand TP
FAU - DeWeese, C
AU  - DeWeese C
FAU - Landin-Olsson, M
AU  - Landin-Olsson M
FAU - Kockum, I
AU  - Kockum I
FAU - Dahlquist, G
AU  - Dahlquist G
FAU - Sundkvist, G
AU  - Sundkvist G
FAU - Stenger, D
AU  - Stenger D
FAU - Lernmark, A
AU  - Lernmark A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Amino Acids)
RN  - 0 (HLA-DQ Antigens)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 94ZLA3W45F (Arginine)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Adolescent
MH  - Amino Acid Sequence
MH  - Amino Acids/*analysis/genetics/metabolism
MH  - Arginine/analysis
MH  - Aspartic Acid/analysis
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/*epidemiology/*immunology/metabolism
MH  - Female
MH  - Gene Amplification
MH  - Genotype
MH  - HLA-DQ Antigens/*analysis/chemistry/metabolism
MH  - Humans
MH  - Incidence
MH  - Infant
MH  - Leucine/analysis
MH  - Male
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Polymorphism, Genetic
MH  - Sweden/epidemiology
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 10.2337/diab.44.1.125 [doi]
PST - ppublish
SO  - Diabetes. 1995 Jan;44(1):125-31. doi: 10.2337/diab.44.1.125.