title: HLA-DQ screening for risk assessment of insulin dependent diabetes in northern Italy.
abstract: Genetic markers may be used to improve the prediction of insulin-dependent diabetes mellitus (type 1) in individuals with islet autoantibodies. In order to develop a risk assessment strategy for the Lombardy region of northern Italy based on genetic and immunological markers, we analyzed HLA DQA1 and DQB1 alleles in 60 type 1 probands and their first-degree relatives and 65 unrelated control subjects from the same area using polymerase chain reaction (PCR) and oligonucleotide probes. The major risk haplotypes were DQA1 *0501-DQB1*0201 (39.1% of diabetic vs. 8.9% of non-diabetic haplotypes) and DQA1 *0301-DQB1*0302(20% of diabetic vs 7.1% of non-diabetic haplotypes). Stratified analysis showed DQA1*0102-DQB1*0502 also to be associated with type 1 susceptibility when found together with DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302. One type 1 patient had the type 1-protective DQA1*0102-DQB1*0602 haplotype. Overall, 88% of patients and 20% of unrelated control subjects had either DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302 in the absence of DQA1*0102-DQB1*0602. These data suggest that typing for markers identifying these three haplotypes in the Lombardy population will achieve a sensitivity of almost 90% and exclude 80% of children from subsequent islet autoantibody testing.
authors.affiliation: Department of Laboratory Medicine, Istituto Scientifico San Raffaele, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Lampasona
authors.forename: M
authors.initials: M
authors.lastname: Ferrari
authors.forename: E
authors.initials: E
authors.lastname: Bonifacio
authors.forename: M R
authors.initials: MR
authors.lastname: Pastore
authors.forename: P
authors.initials: P
authors.lastname: Carrera
authors.forename: A
authors.initials: A
authors.lastname: Sergi
authors.forename: S
authors.initials: S
authors.lastname: Genovese
authors.forename: M
authors.initials: M
authors.lastname: Trucco
authors.forename: J
authors.initials: J
authors.lastname: Dorman
authors.forename: E
authors.initials: E
authors.lastname: Bosi
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen