التفاصيل البيبلوغرافية
| العنوان: |
Improving prediction of type 1 diabetes by testing non- HLA genetic variants in addition to HLA markers. |
| المؤلفون: |
Steck, Andrea K1, Dong, Fran1, Wong, Randall1, Fouts, Alexandra1, Liu, Edwin2, Romanos, Jihane3,4, Wijmenga, Cisca3, Norris, Jill M5, Rewers, Marian J1 |
| المصدر: |
Pediatric Diabetes. Aug2014, Vol. 15 Issue 5, p355-362. 8p. |
| مصطلحات موضوعية: |
*DNA, *TYPE 1 diabetes, *BIOMARKERS, *DIABETES, *ETHNIC groups, *EVALUATION of medical care, *PEDIATRICS, *POLYMERASE chain reaction, *RACE, *HLA-B27 antigen, *DIAGNOSIS, *PHYSIOLOGY |
| مستخلص: |
Objective The purpose of this study was to explore whether non-human leukocyte antigen (non- HLA) genetic markers can improve type 1 diabetes ( T1D) prediction in a prospective cohort with high-risk HLA-DR, DQ genotypes. Methods The Diabetes Autoimmunity Study in the Young ( DAISY) follows prospectively for the development of T1D and islet autoimmunity ( IA) children at increased genetic risk. A total of 1709 non-Hispanic White DAISY participants have been genotyped for 27 non- HLA single nucleotide polymorphisms (SNPs) and one microsatellite. Results In multivariate analyses adjusting for family history and HLA-DR3/4 genotype, PTPN22 (rs2476601) and two UBASH3A (rs11203203 and rs9976767) SNPs were associated with development of IA [hazard ratio ( HR) = 1.87, 1.55, and 1.54, respectively, all p ≤ 0.003], while GLIS3 and IL2RA showed borderline association with development of IA. INS, UBASH3A, and IFIH1 were significantly associated with progression from IA to diabetes ( HR=1.65, 1.44, and 1.47, respectively, all p ≤ 0.04), while PTPN22 and IL27 showed borderline association with progression from IA to diabetes. In survival analysis, 45% of general population DAISY children with PTPN22 rs2476601 TT or HLA-DR3/4 and UBASH3A rs11203203 AA developed diabetes by age 15, compared with 3% of children with all other genotypes (p < 0.0001). Addition of non- HLA markers to HLA-DR3/4, DQ8 did not improve diabetes prediction in first-degree relatives. Conclusion Addition of PTPN22 and UBASH3A SNPs to HLA-DR, DQ genotyping can improve T1D risk prediction. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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