title: [Alleles of HLA-DQB1 and familial aggregation of type 1 diabetes].
abstract: The HLA complex, located on the short arm of chromosome 6, is the strongest genetic marker for type 1 diabetes (T1DM). In previous study we demonstrated association between genes HLA-DRB1 and HLA-DQB1 and T1DM in the Polish population. There is a strong-independent association of alleles HLA-DRB1*0401 and DQB1*302, despite population linkage disequilibrium among alleles of these genes. The aim of the current study was to verify a hypothesis that some alleles or haplotypes of HLA-DRB1, DQA1 and DQB1 genes increase the risk for familiar aggregation of T1DM. We analysed 507 patients with IDDM derived from 80 multiplex and 325 patients from simplex families. PCR and hybridisation with SSO probes performed HLA typing for DRB1, DQA1 and DQB1 alleles. Genetic analysis demonstrated strong association of allele HLA-DQB1*0302 with T1DM in the Polish population in families with single (DM1) and more numerous cases (DM2) cases, compared with healthy cases (n=103). The HLA-DQB1*302 allele frequencies were 27.8% vs 8.7%; Pc<10(-5); OR(95%CI)=4,03(3.80-4.25) and 16.3% vs 8.7%; Pc<0.04; OR(95%CI)=2.04(1.79-2.89), respectively. The presence of allele HLA-DQB1*0602 has a strong protective effect from T1DM in both studied groups (1.46% vs. 13.6%; Pc<10(-5); OR(95%CI)=0.09(-0.25-0.44) and 0.98% vs. 13.6%; Pc<10(-5); OR(95%CI)=0.06(-0.46-0.58), respectively. Interestingly, HLA-DRB1*04 allele more often co-segregated with DM2 families as comparing the DM1 group (31.0% vs. 15.8%, respectively; Pc<10(-5)). However in both cases differences remain significant as compared to controls: Pc<10(-5), OR (95%CI)=3.52(3.33-3.70) and Pc<10(-5) OR(95%CI)=6.17(5.97-6.37), for DM1 and DM2 respectively. Subtyping of HLA-DRB1*04 alleles demonstrated that the strongest predisposing effect has been identified with DRB1*0401. Moreover, difference in frequencies of the protective allele HLA-DQB1*0301 among DM1 and DM2 group was revealed (8.8% vs. 13.7%, respectively; Pc<10(-5)) and the protective effect of this allele remained only significant in DM1 group: 8.8% vs. 19.9%; Pc<10(-5); OR(95%CI)=0.39(0.19-0.58). The results suggest that it is likely that familial aggregation of T1DM is associated with lower frequency of protective alleles of HLA-DQB1 gene.
authors.affiliation: Klinika Chorób Dzieci, Instytut Pediatrii, Akademia Medyczna, ul. Sporna 36/50, 91-738 Łódź, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Kubryn
authors.forename: Wojciech
authors.initials: W
authors.lastname: Młynarski
authors.forename: Hanna
authors.initials: H
authors.lastname: Trippenbach-Dulska
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Szalecki
authors.forename: Lucyna
authors.initials: L
authors.lastname: Lisowicz
authors.forename: Barbara
authors.initials: B
authors.lastname: Surdej
authors.forename: Olgierd
authors.initials: O
authors.lastname: Pilecki
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Heinrich
authors.forename: Krystyna
authors.initials: K
authors.lastname: Wyka
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Perenc
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bodalski
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D011044:Poland; D016133:Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen