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

Lucas Nygård; Antti-Pekka Laine; Minna Kiviniemi; Jorma Toppari; Taina Härkönen; Mikael Knip; Riitta Veijola; Johanna Lempainen; Jorma Ilonen

doi:10.1016/j.humimm.2021.07.010

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.

Authors

Lucas Nygård¹, Antti-Pekka Laine², Minna Kiviniemi², Jorma Toppari³, Taina Härkönen⁴, Mikael Knip⁵, Riitta Veijola⁶, Johanna Lempainen², Jorma Ilonen⁷

Affiliations

¹ Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland; Faculty of Science and Engineering, Cell Biology, Åbo Akademi, Turku, Finland.
² Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
³ Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, and Centre for Population Health Research, University of Turku, Turku, Finland.
⁴ Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
⁵ Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
⁶ Department of Paediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland.
⁷ Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland. Electronic address: jorma.ilonen@utu.fi.

PMID: 34311991
DOI: 10.1016/j.humimm.2021.07.010

Abstract

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*

Substances

HLA-DRB1 Chains