title: Genetic prediction of autoimmunity: initial oligogenic prediction of anti-islet autoimmunity amongst DR3/DR4-DQ8 relatives of patients with type 1A diabetes.
abstract: In this study, the combined risk for expressing anti-islet autoantibodies and type 1A diabetes (T1D) was prospectively examined in 85 sampled relatives who had the high-risk HLA genotype (DR3-DQ8 DR4-DQ2). An insulin gene polymorphism, -23 HphI, and a lymphocyte tyrosine phosphatase gene polymorphism at position 1858C>T (amino acid 620 Arg to Trp), PTPN22/LYP, were analyzed. Life tables were created evaluating time to anti-islet autoantibody development and T1D. Of relatives with the high-risk HLA type followed for 3years, 9 of 43 (28.1%) with the high-risk -23 HphI polymorphism developed anti-islet autoantibodies versus two of 36 (5.6%) relatives with the lower-risk -23 HphI genotypes (p=0.048). Of relatives with the high-risk HLA type followed for 5years, eight of 32 (25.0%) with the high-risk -23 HphI polymorphism (A/A) developed T1D versus zero of 26 (0%) relatives with the lower-risk -23 HphI genotypes (A/T and T/T) (p=0.006). The PTPN22/LYP polymorphism, with genotypes C/C, C/T, and T/T, did not show a significant difference in risk by genotype. These results highlight the multiplicative risk of combined high-risk genotypes at different loci in terms of time to autoantibody and autoimmune disease development.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Avenue B-140, Denver, CO 80262, USA. theresa.aly@uchsc.edu
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Aly
authors.forename: Akane
authors.initials: A
authors.lastname: Ide
authors.forename: Kurt
authors.initials: K
authors.lastname: Humphrey
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Barker
authors.forename: Andrea
authors.initials: A
authors.lastname: Steck
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Redondo
authors.forename: Kim
authors.initials: K
authors.lastname: McFann
authors.forename: Christine M
authors.initials: CM
authors.lastname: Roberts
authors.forename: Sunanda R
authors.initials: SR
authors.lastname: Babu
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Rewers
mesh_terms: D000293:Adolescent; D015551:Autoimmunity / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005192:Family Health; D005820:Genetic Testing; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens