HLA-DQ and HLA-DRB1 alleles associated with Henoch-Schonlein purpura nephritis in Finnish pediatric population : a genome-wide association study

Näytä kaikki kuvailutiedot



Pysyväisosoite

http://hdl.handle.net/10138/340177

Lähdeviite

Koskela , M , Nihtilä , J , Ylinen , E , Kolho , K-L , Nuutinen , M , Ritari , J & Jahnukainen , T 2021 , ' HLA-DQ and HLA-DRB1 alleles associated with Henoch-Schonlein purpura nephritis in Finnish pediatric population : a genome-wide association study ' , Pediatric Nephrology , vol. 36 , no. 8 , pp. 2311-2318 . https://doi.org/10.1007/s00467-021-04955-7

Julkaisun nimi: HLA-DQ and HLA-DRB1 alleles associated with Henoch-Schonlein purpura nephritis in Finnish pediatric population : a genome-wide association study
Tekijä: Koskela, Mikael; Nihtilä, Julia; Ylinen, Elisa; Kolho, Kaija-Leena; Nuutinen, Matti; Ritari, Jarmo; Jahnukainen, Timo
Tekijän organisaatio: Children's Hospital
HUS Children and Adolescents
University of Helsinki
Helsinki University Hospital Area
Clinicum
University Management
Päiväys: 2021-08
Kieli: eng
Sivumäärä: 8
Kuuluu julkaisusarjaan: Pediatric Nephrology
ISSN: 0931-041X
DOI-tunniste: https://doi.org/10.1007/s00467-021-04955-7
URI: http://hdl.handle.net/10138/340177
Tiivistelmä: Background The pathophysiology of Henoch-Schonlein purpura (HSP) is still unclear, but several findings suggest that genetic factors may influence disease susceptibility. We aimed to perform a genome-wide association study (GWAS) in pediatric HSP patients with an emphasis on severe HSP nephritis. Methods The study included 46 HSP patients, 42 of whom had undergone kidney biopsy. Forty-nine pediatric patients with an inflammatory bowel disease (IBD) served as an autoimmune disease control group while Finnish bone marrow and blood donors represented the general reference population (n = 18,757). GWAS was performed for HSP and IBD samples in a case-control manner against the reference population. The analysis also included imputation of human leukocyte antigen (HLA) alleles. Results GWAS analysis in HSP revealed several polymorphisms from the HLA region that surpassed the genome-wide significance level. Three HLA class II alleles were also significantly more frequent in HSP than in the reference population: DQA1*01:01, DQB1*05:01, and DRB1*01:01. Haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 occurred in 43.5% of HSP patients, whereas its frequency was 8.2% in IBD patients and 15.0% in the reference population. HSP patients with this haplotype showed similar baseline clinical findings and outcome as HSP patients negative for the haplotype. In IBD patients, no polymorphism or HLA allele appeared significant at the genome-wide level. Conclusions Our results suggest that haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 is associated with susceptibility to HSP, but not with the severity of the kidney involvement. These HLA associations did not occur in IBD patients, suggesting that they are specific to HSP and not related to susceptibility to autoimmune diseases in general.
Avainsanat: Crohn's disease
Inflammatory bowel disease
Children
Genetics
IgA vasculitis
3123 Gynaecology and paediatrics
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


Tiedostot

Latausmäärä yhteensä: Ladataan...

Tiedosto(t) Koko Formaatti Näytä
Koskela2021_Art ... dHLA_DRB1AllelesAssoci.pdf 625.9KB PDF Avaa tiedosto

Viite kuuluu kokoelmiin:

Näytä kaikki kuvailutiedot