The association of HLA-DP loci with autoimmune diabetes in Chinese

Diabetes Res Clin Pract. 2021 Mar:173:108582. doi: 10.1016/j.diabres.2020.108582. Epub 2020 Dec 8.

Abstract

Aims: To determine if HLA-DP loci independently contribute to classic type 1 diabetes (T1D) of all ages, childhood-onset T1D and latent autoimmune diabetes in adults (LADA) among Chinese Han population.

Methods: A total of 518 patients with classic T1D (Among them 180 participants manifested T1D between 1 and 14 years), 519 patients with LADA and 527 normal controls were genotyped for both HLA-DPA1 and -DPB1 loci. The frequencies of DP alleles and haplotypes in patients were directly compared to those in controls, followed by adjustment for linkage disequilibrium (LD) with DR-DQ haplotypes.

Results: In the direct comparison, DPA1*01:03, DPB1*04:01 and DPA1*01:03-DPB1*04:01 showed disease-predisposing effects in both the overall T1D group and the childhood-onset T1D group mainly due to their conjunction with the known susceptible DR3 haplotype. Conditioning on DR-DQ haplotypes, only DPA1*02:02-DPB1*02:02 significantly increased T1D risk among those diagnosed during childhood (OR = 2.02, 95% CI = 1.35-3.01). Whether or not adjusted for LD, no statistically significant HLA-DP association could be observed for LADA.

Conclusion: HLA-DP is implicated in the pathogenesis of childhood-onset T1D in Chinese, independent of the predominant DR-DQ loci and might serve as additional markers in genetic models for the recognition of those genetically at-risk individuals.

Keywords: Chinese; Genetics; HLA-DP; Latent autoimmune diabetes in adults; Type 1 diabetes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • China
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Gene Frequency / genetics*
  • Genetic Loci / genetics*
  • HLA-DP beta-Chains / genetics*
  • Humans
  • Infant
  • Latent Autoimmune Diabetes in Adults / genetics*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • HLA-DP beta-Chains