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Titolo:
POLYMORPHIC AMINO-ACID VARIATIONS IN HLA-DQ ARE ASSOCIATED WITH SYSTEMATIC PHYSICAL PROPERTY CHANGES AND OCCURRENCE OF IDDM
Autore:
SANJEEVI CB; LYBRAND TP; DEWEESE C; LANDINOLSSON M; KOCKUM I; DAHLQUIST G; SUNDKVIST G; STENGER D; LERNMARK A;
Indirizzi:
KAROLINSKA HOSP & INST,DEPT MOLEC MED,L1 02 S-17176 STOCKHOLM SWEDEN UNIV WASHINGTON,CTR BIOENGN SEATTLE WA 98195 LUND UNIV,DEPT MED LUND SWEDEN UMEA UNIV,DEPT PEDIAT UMEA SWEDEN UMEA UNIV,DEPT EPIDEMIOL & HLTH CARE RES S-90187 UMEA SWEDEN LUND UNIV,MALMO GEN HOSP,DEPT MED S-21401 MALMO SWEDEN UNIV WASHINGTON,DEPT MED,RH WILLIAMS LAB SEATTLE WA 00000
Titolo Testata:
Diabetes
fascicolo: 1, volume: 44, anno: 1995,
pagine: 125 - 131
SICI:
0012-1797(1995)44:1<125:PAVIHA>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT DIABETES-MELLITUS; SUSCEPTIBILITY; RESISTANCE; MOLECULES; PROTEINS; JAPANESE; HLA-DQA1; COMPLEX; PACKING; RISK;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
C.B. Sanjeevi et al., "POLYMORPHIC AMINO-ACID VARIATIONS IN HLA-DQ ARE ASSOCIATED WITH SYSTEMATIC PHYSICAL PROPERTY CHANGES AND OCCURRENCE OF IDDM", Diabetes, 44(1), 1995, pp. 125-131

Abstract

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 367matched control subjects, As many as 97% of patients compared with 75% of control subjects were positive for one or several of DQA10301, DQA10501, DQB1*0302, or DQB1*0201. Asp-57 DQB was present among 28% ofpatients, 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, DQA10301-DQB1*0302 (DQ8) and DQA10301-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 physicochemical 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.

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Documento generato il 05/12/20 alle ore 13:51:36