The unfavorable impact of DR9/DR9 genotype on the frequency and quality of partial remission in type 1 diabetes.

CONTEXT Partial remission (PR) is a specific stage in type 1 diabetes (T1D). Although human leukocyte antigen (HLA) class II loci are the strongest genetic determinants in T1D, the relationship between PR and HLA remains unclear. OBJECTIVE To investigate the association between PR status and HLA genotypes in T1D patients. METHODS A total of 237 T1D patients were included. PR was defined according to C-peptide ≥300 pmol/L. The frequency of PR and peak C-peptide levels during remission phase were compared according to HLA status. Clinical characteristics including age of onset and diabetes autoantibodies were collected. All analyses were duplicated when subjects were divided into childhood- and adult-onset T1D. RESULTS The median follow-up time was 24 months, 65.8% (156/237) of T1D patients went into PR. DR9/DR9 carriers had lower PR rate (44.2% vs. 70.6%, P=0.001) and less likely to enter PR (OR=0.218, 95% CI: 0.098-0.487, P<0.001) than the non-DR9/DR9 carriers, observed in both childhood- and adult-onset T1D. Besides, the peak C-peptide during PR phase was also lower in DR9/DR9 carriers, more notable in adult-onset T1D. When compared with non-DR9/DR9 carriers, T1D with DR9/DR9 genotype presented an older age of onset and a lower positivity of zinc transporter 8 antibody (ZnT8A), and the lower trend of ZnT8A was only found in adult-onset T1D (P=0.049). CONCLUSIONS T1D carrying susceptible DR9/DR9 are less prone to undergo PR. Additionally, the recovery extent of β-cell function during the PR phase tends to be lower in adults carrying DR9/DR9, which might be associated with ZnT8A.