{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Johnson K"],"funding":["NIDDK NIH HHS"],"pagination":["611-5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4886718"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(8)"],"pubmed_abstract":["OBJECTIVE:To evaluate UBASH3A (rs11203203) as a predictor of persistent islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS:The Diabetes Autoimmunity Study in the Young (DAISY) followed prospectively for development of persistent IA (autoantibodies to insulin, GAD65, IA-2, or ZnT8 on at least two consecutive exams) and diabetes 1715 non-Hispanic white children at increased genetic risk for T1D. The DAISY participants were genotyped for rs11202203 (UBASH3A). RESULTS:UBASH3A allele A was associated with development of IA [hazard ratio (HR)?=?1.46, 95%CI?=?1.11-1.91, p?=?0.007] and diabetes (HR?=?1.84, 95%CI?=?1.28-2.64, p?=?0.001), controlling for presence of HLA-DR3/4,DQB1*0302 and having a first-degree relative (FDR) with T1D. The UBASH3A AA genotype conferred higher risk of persistent IA (12.7%) and diabetes (6.1%) by age 10 than for AG (7.7 and 3.1%, respectively) or GG (5.3 and 2.0%) genotype (p?=?0.009 for IA, p?=?0.0004 for diabetes). Among children with no family history of T1D, but HLA-DR3/4,DQB1*0302 and UBASH3A AA genotype, 35.9% developed IA and 50.6% developed diabetes by age 15. CONCLUSIONS:UBASH3A appears to be an independent predictor of IA and T1D in children, including those free of family history of T1D but carrying the HLA-DR3/4,DQB1*0302 genotype. If confirmed, UBASH3A may prove useful in T1D risk prediction and pre-screening of the general population children for clinical trials."],"journal":["Pediatric diabetes"],"pubmed_title":["rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes."],"pmcid":["PMC4886718"],"funding_grant_id":["K12 DK063722","P30 DK057516","P30 DK57516","R37 DK32493","R37 DK032493","5 K12 DK63722."],"pubmed_authors":["Johnson K","Ziegler AG","Barriga KJ","Wong R","Rewers MJ","Klingensmith G","Steck AK"],"additional_accession":[]},"is_claimable":false,"name":"rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes.","description":"OBJECTIVE:To evaluate UBASH3A (rs11203203) as a predictor of persistent islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS:The Diabetes Autoimmunity Study in the Young (DAISY) followed prospectively for development of persistent IA (autoantibodies to insulin, GAD65, IA-2, or ZnT8 on at least two consecutive exams) and diabetes 1715 non-Hispanic white children at increased genetic risk for T1D. The DAISY participants were genotyped for rs11202203 (UBASH3A). RESULTS:UBASH3A allele A was associated with development of IA [hazard ratio (HR)?=?1.46, 95%CI?=?1.11-1.91, p?=?0.007] and diabetes (HR?=?1.84, 95%CI?=?1.28-2.64, p?=?0.001), controlling for presence of HLA-DR3/4,DQB1*0302 and having a first-degree relative (FDR) with T1D. The UBASH3A AA genotype conferred higher risk of persistent IA (12.7%) and diabetes (6.1%) by age 10 than for AG (7.7 and 3.1%, respectively) or GG (5.3 and 2.0%) genotype (p?=?0.009 for IA, p?=?0.0004 for diabetes). Among children with no family history of T1D, but HLA-DR3/4,DQB1*0302 and UBASH3A AA genotype, 35.9% developed IA and 50.6% developed diabetes by age 15. CONCLUSIONS:UBASH3A appears to be an independent predictor of IA and T1D in children, including those free of family history of T1D but carrying the HLA-DR3/4,DQB1*0302 genotype. If confirmed, UBASH3A may prove useful in T1D risk prediction and pre-screening of the general population children for clinical trials.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Dec","modification":"2021-02-19T10:57:15Z","creation":"2019-03-27T02:14:51Z"},"accession":"S-EPMC4886718","cross_references":{"pubmed":["22776074"],"doi":["10.1111/j.1399-5448.2012.00888.x"]}}