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Titolo:
Complex interaction between HLA DR and DO in conferring risk for childhoodtype 1 diabetes
Autore:
Kockum, I; Sanjeevi, CB; Eastman, S; Landin-Olsson, M; Dahlquist, G; Lernmark, A;
Indirizzi:
Univ Washington, Dept Med, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 ton, Dept Med, Seattle, WA 98195 USA Umea Univ, Dept Paediat, Umea, Sweden Umea Univ Umea SwedenUmea Univ, Dept Paediat, Umea, Sweden Univ Lund, Dept Med, Lund, Sweden Univ Lund Lund SwedenUniv Lund, Dept Med, Lund, Sweden Karolinska Inst, Dept Mol Med, Stockholm, Sweden Karolinska Inst Stockholm Sweden Inst, Dept Mol Med, Stockholm, Sweden
Titolo Testata:
EUROPEAN JOURNAL OF IMMUNOGENETICS
fascicolo: 5, volume: 26, anno: 1999,
pagine: 361 - 372
SICI:
0960-7420(199910)26:5<361:CIBHDA>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLASS-II ALLELES; DQ-BETA CHAIN; PRIMARY ASSOCIATION; GENETIC-ANALYSIS; IDDM SUSCEPTIBILITY; CHINESE POPULATION; PCR AMPLIFICATION; SWEDISH CHILDREN; UNITED-KINGDOM; CASE-REFERENT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
86
Recensione:
Indirizzi per estratti:
Indirizzo: Lernmark, A Univ Washington, Dept Med, Box 357710, Seattle, WA 98195 USA Univ Washington Box 357710 Seattle WA USA 98195 , WA 98195 USA
Citazione:
I. Kockum et al., "Complex interaction between HLA DR and DO in conferring risk for childhoodtype 1 diabetes", EUR J IMM, 26(5), 1999, pp. 361-372

Abstract

Type 1 (insulin-dependent) diabetes mellitus is associated with HLA DR andDQ factors, but the primary risk alleles are difficult to identify becauserecombination events are rare in the DQ-DR region. The risk of HLA genotypes for type 1 diabetes was therefore studied in more than 420 incident new onset, population-based type 1 diabetes children and 340 age, sex and geographically matched controls from Sweden. A stepwise approach was used to analyse risk by relative and absolute risks, stratification analysis and the predispositional allele test. The strongest relative and absolute risks wereobserved for DQB1*02-DQA1*0501/DQB1*'0302-DQA1*0301 heterozygotes (AR 1/46, P < 0.001) or the simultaneous presence of both DRB1*03 and DQB1*0302 (AR1/52, P < 0.001). Stratification analysis showed that DQB1*0302 was more frequent among DRB1*04 patients than DRB1*04 controls (P < 0.001), while DRB1*03 was more frequent among both DQA1*0501 (P < 0.001) and DQB1*02 (P < 0.001) patients than respective controls. The predispositional allele test indicated that DRB1*03 (P < 0.001) would be the predominant risk factor on the DRB1*03-DQA1*0501-DQB1*02 haplotype. In contrast, although DQB1*0302 (P <0.001) would be the pre dominant risk factor on the DRB1*04-DQA1*0301-DQB1*0302 haplotype, the predispositional allele test also showed that DRB1*0401, but no other DRB1*04 subtype, had an additive risk to that of DQB1*0302 (P < 0.002). It is concluded that the association between type 1 diabetes and HLA is due to a complex interaction between DR and DQ since (1) DRB1*03 was more strongly associated with the disease than DQA1*0501-DQB1*02 and (2) DRB1*0401 had an additive effect to DQB1*0302. The data from this population-based investigation suggest an independent role of DR in the risk of developing type 1 diabetes, perhaps by providing diseases-promoting transcomplementation molecules.

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Documento generato il 04/12/20 alle ore 13:15:04