PMID- 33591409
OWN - NLM
STAT- MEDLINE
DCOM- 20220215
LR  - 20230320
IS  - 1432-198X (Electronic)
IS  - 0931-041X (Print)
IS  - 0931-041X (Linking)
VI  - 36
IP  - 8
DP  - 2021 Aug
TI  - HLA-DQ and HLA-DRB1 alleles associated with Henoch-Schonlein purpura nephritis in 
      Finnish pediatric population: a genome-wide association study.
PG  - 2311-2318
LID - 10.1007/s00467-021-04955-7 [doi]
AB  - 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.
FAU - Koskela, Mikael
AU  - Koskela M
AD  - Children's Hospital, Pediatric Research Center, University of Helsinki, Helsinki 
      University Hospital, Helsinki, Finland. mikael.koskela@helsinki.fi.
AD  - Department of Pediatric Nephrology and Transplantation, New Children's Hospital, 
      University of Helsinki and Helsinki University Hospital, PO Box 347, 
      Stenbackinkatu 9, 00029 HUS, Helsinki, Finland. mikael.koskela@helsinki.fi.
FAU - Nihtila, Julia
AU  - Nihtila J
AD  - University of Helsinki, Helsinki, Finland.
AD  - Finnish Red Cross Blood Service, Helsinki, Finland.
FAU - Ylinen, Elisa
AU  - Ylinen E
AD  - Department of Pediatric Nephrology and Transplantation, New Children's Hospital, 
      University of Helsinki and Helsinki University Hospital, PO Box 347, 
      Stenbackinkatu 9, 00029 HUS, Helsinki, Finland.
FAU - Kolho, Kaija-Leena
AU  - Kolho KL
AD  - Children's Hospital, Pediatric Research Center, University of Helsinki, Helsinki 
      University Hospital, Helsinki, Finland.
AD  - Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
FAU - Nuutinen, Matti
AU  - Nuutinen M
AD  - Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.
AD  - PEDEGO Research Unit, Research Unit for Pediatrics, Dermatology, Clinical 
      Genetics, Obstetrics and Gynecology, Medical Research Center Oulu (MRC Oulu), 
      Oulu, Finland.
FAU - Ritari, Jarmo
AU  - Ritari J
AD  - Finnish Red Cross Blood Service, Helsinki, Finland.
FAU - Jahnukainen, Timo
AU  - Jahnukainen T
AD  - Department of Pediatric Nephrology and Transplantation, New Children's Hospital, 
      University of Helsinki and Helsinki University Hospital, PO Box 347, 
      Stenbackinkatu 9, 00029 HUS, Helsinki, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210216
PL  - Germany
TA  - Pediatr Nephrol
JT  - Pediatric nephrology (Berlin, Germany)
JID - 8708728
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Alleles
MH  - Child
MH  - Finland
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DRB1 Chains/*genetics
MH  - Haplotypes
MH  - Humans
MH  - *IgA Vasculitis/genetics
MH  - *Inflammatory Bowel Diseases
MH  - *Nephritis/genetics
PMC - PMC8260528
OTO - NOTNLM
OT  - Children
OT  - Crohn's disease
OT  - Genetics
OT  - IgA vasculitis
OT  - Inflammatory bowel disease
COIS- The authors declare no conflict of interest.
EDAT- 2021/02/17 06:00
MHDA- 2022/02/16 06:00
PMCR- 2021/02/16
CRDT- 2021/02/16 12:10
PHST- 2020/11/23 00:00 [received]
PHST- 2021/01/19 00:00 [accepted]
PHST- 2020/12/18 00:00 [revised]
PHST- 2021/02/17 06:00 [pubmed]
PHST- 2022/02/16 06:00 [medline]
PHST- 2021/02/16 12:10 [entrez]
PHST- 2021/02/16 00:00 [pmc-release]
AID - 10.1007/s00467-021-04955-7 [pii]
AID - 4955 [pii]
AID - 10.1007/s00467-021-04955-7 [doi]
PST - ppublish
SO  - Pediatr Nephrol. 2021 Aug;36(8):2311-2318. doi: 10.1007/s00467-021-04955-7. Epub 
      2021 Feb 16.