rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes
Article first published online: 8 JUL 2012
© 2012 John Wiley & Sons A/S
Volume 13, Issue 8, pages 611–615, December 2012
How to Cite
rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes., , , , , , .
- Issue published online: 22 NOV 2012
- Article first published online: 8 JUL 2012
- Manuscript Accepted: 15 MAY 2012
- Manuscript Revised: 8 MAR 2012
- Manuscript Received: 3 JAN 2012
- NIH grants. Grant Numbers: R37 DK32493, P30 DK57516, 5 K12 DK63722
- JDRF Grant 11-2010-206 Early Career Patient-oriented Diabetes Award
- islet autoimmunity;
- type 1 diabetes;
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).
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.
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.