Tri-SNP polymorphism in the intron of HLA-DRA1 affects type 1 diabetes susceptibility in the Finnish population

Hum Immunol. 2021 Dec;82(12):912-916. doi: 10.1016/j.humimm.2021.07.010. Epub 2021 Jul 24.


Genes in the HLA class II region include the most important inherited risk factors for type 1 diabetes (T1D) although also polymorphisms outside the HLA region modulate the predisposition to T1D. This study set out to confirm a recent observation in which a novel expression quantitative trait locus was formed by three single nucleotide polymorphisms (SNP) in the intron of HLA-DRA1 in DR3-DQ2 haplotypes. The SNPs significantly increased the risk for T1D in DR3-DQ2 homozygous individuals and we intended to further explore this association, in the Finnish population, by comparing two DR3-DQ2 positive genotypes. Cohorts with DR3-DQ2/DR3-DQ2 (N = 570) and DR3-DQ2/DR1-DQ5 (N = 1035) genotypes were studied using TaqMan analysis that typed for rs3135394, rs9268645 and rs3129877. The tri-SNP haplotype was significantly more common in cases than controls in the DR3-DQ2/DR3-DQ2 cohort (OR = 1.70 CI 95% = 1.15-2.51P = 0.007). However, no significant associations could be observed in the DR3-DQ2/DR1-DQ5 cohort.

Keywords: Expression quantitative trait locus; Finland; HLA-DR3; Single nucleotide polymorphism; Type 1 diabetes.

MeSH terms

  • Diabetes Mellitus, Type 1* / genetics
  • Diabetes Mellitus, Type 1* / immunology
  • Female
  • Finland
  • Genetic Predisposition to Disease*
  • HLA-DRB1 Chains* / genetics
  • HLA-DRB1 Chains* / immunology
  • Humans
  • Introns*
  • Male
  • Polymorphism, Single Nucleotide*


  • HLA-DRB1 Chains