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Pediatr Diabetes. 2012 Dec;13(8):611-5. doi: 10.1111/j.1399-5448.2012.00888.x. Epub 2012 Jul 8.

rs11203203 is associated with type 1 diabetes risk in population pre-screened for high-risk HLA-DR,DQ genotypes.

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  • 1Barbara Davis Center for Childhood Diabetes, University of Colorado Denver (UCD), Aurora, CO 80045, USA.

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.

© 2012 John Wiley & Sons A/S.

PMID:
22776074
[PubMed - indexed for MEDLINE]
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