Adult‐onset type 1 diabetic patients with less severe clinical manifestation have less risk DR‐DQ genotypes than childhood‐onset patients

Abstract

BackgroundThe aim of this study was to investigate differences in clinical features and HLA genotypes between adult‐onset and childhood‐onset patients with type 1 diabetes in a Chinese population.Materials and MethodsThis study enrolled 716 Han Chinese patients with type 1 diabetes from Guangdong (258 childhood‐onset and 458 adult‐onset) to compare their clinical features. Of them 214 patients with classical type 1 diabetes (100 childhood‐onset and 114 adult‐onset) were selected for HLA DR and DQ genotyping by next‐generation sequencing.ResultsAdult‐onset patients were characterized by longer duration of symptoms before diagnosis, lower frequency of DKA at disease onset, less frequent autoantibody positivity, higher serum C‐peptide concentrations, and better glycemic control. These findings were replicated in the restricted cohort of 214 patients with classical type 1 diabetes. Compared with childhood‐onset patients, adult‐onset patients had a lower frequency of the DR9 haplotype, as well as lower frequency of high‐risk DR3/DR4 and DR3/DR9 genotypes, but higher frequency of DR3/DR3 genotype and DR3/X, DR4/X or DR9/X (X, non‐risk) genotypes.ConclusionsAdult‐onset type 1 diabetic patients with susceptible haplotypes (DR3, DR4 or DR9) were more likely to carry protective DR‐DQ haplotypes than childhood‐onset patients, which suggested the association between less risk DR‐DQ genotypes and the less severe clinical manifestation in adult‐onset patients.

HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes

“…It has been reported that European patients with younger onset age had a higher frequency of the susceptible DRB1*03:01-DQB1*02:01/DRB1*04 -DQ8 genotype, but a lower frequency of the protective DRB1*15:01-DQB1*06:02 and DRB1*07:01-DQB1*03:03 haplotypes than those with older onset age [14]. Our previous study in Chinese patients showed that, compared with childhood-onset patients, adult-onset patients had a lower frequency of the high-risk DR3/DR4 and DR3/DR9 genotypes, but higher frequency of DR3/DR3 genotype and DR3/X, DR4/X, or DR9/X (X, non-risk) genotypes [11].…”

“…The strong contributions of HLA-DR and -DQ genes to type 1 diabetes, and the extremely high LD within the HLA region emphasise the importance of adjustment or stratification for DR-DQ when analysing the effects of additional susceptibility genes. Our recent study showed that, compared with childhood-onset patients, adult-onset patients had milder clinical features and a lower frequency of high-risk DR3/DR4 and DR3/DR9 genotypes [11]. Based on our previous study, we expanded the sample size and did linear regression analyses of DR-DQ in patients through all onset ages in the current study.…”

“…Based on our previous study, which mainly focused on the effects of DR-DQ on the classical type 1 diabetes with different onset ages [11], this study intended to extend the analysis of HLA genes beyond the classical class II genes to investigate the effects of HLA class I genes in a larger dataset and to explore the association of HLA genes with islet autoantibodies in a dataset with autoantibody negative participants included. Therefore, in addition to the cases of classical type 1 diabetes included in our previous study [11], we expanded the sample size without setting additional selection criteria to restrict DKA or autoantibody status. As a result, a total of 361 patients currently with data available were included in this study (electronic supplementary material [ESM] Fig.…”

“…In China, our recent nationwide epidemiological study for all ages found that almost 65% of the newly diagnosed type 1 diabetes cases occurred in adults [8]. Previous studies showed that compared with childhoodonset patients, adult-onset patients had less aggressive disease onset, less severe clinical manifestation, lower frequency of diabetic autoantibodies and lower DR-DQ risk load [9][10][11][12][13][14]. It has been reported that European patients with younger onset age had a higher frequency of the susceptible DRB1*03:01-DQB1*02:01/DRB1*04 -DQ8 genotype, but a lower frequency of the protective DRB1*15:01-DQB1*06:02 and DRB1*07:01-DQB1*03:03 haplotypes than those with older onset age [14].…”

Three‐phasic pattern of C‐peptide decline in type 1 diabetes patients with partial remission

“…All subjects were genotyped by sequencing exon 2 of each gene yielded two‐ or four‐digit resolution for HLA‐DQA1 and four‐digit resolution for HLA‐DQB1 and HLA‐DRB1. According to the previous research, DR3 (DRB1 * 03:01:01‐DQA1 * 05:01:01‐DQB1 * 02:01:01), DR4 (DRB1 * 04:05:01‐DQA1 * 03:03:01‐ DQB1 * 04:01:01, DRB1 * 04:05:01‐DQA1 * 03:01:01‐DQB1 * 03:02:01 and DRB1 * 04:05:01‐DQA1 * 03:03:01‐DQB1 * 03:02:01) and DR9 (DRB1 * 09:01:02‐DQA1 * 03:02‐DQB1 * 03:03:02) were haplotypes associated with T1D susceptibility in Chinese 13 . Non‐susceptible haplotype was defined as DRX where x was not DR3, DR4 or DR9.…”