Advanced

Next generation sequencing reveals that HLA-DRB3, -DRB4 and -DRB5 may be associated with islet autoantibodies and risk for childhood type 1 diabetes.

Zhao, Lue Ping; Alshiekh, Shehab LU ; Carlsson, Annelie LU ; Larsson, Helena LU ; Forsander, Gun; Ivarsson, Sten LU ; Ludvigsson, Johnny; Kockum, Ingrid; Marcus, Claude and Persson, Martina, et al. (2016) In Diabetes 65(3). p.710-718
Abstract
The possible contribution of HLA-DRB3, -DRB4 and -DRB5 alleles to type 1 diabetes risk and to autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A) or ZnT8 against either of the three amino acid variants, R, W or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next generation sequencing (NGS) was therefore used to determine all DRB alleles in consecutively diagnosed, islet autoantibody positive 1-18 years old type 1 diabetes patients (n=970) and controls (n=448). It was tested whether DRB3, DRB4 or DRB5 alleles were associated with the risk of DRB1 for autoantibodies, type 1 diabetes, or both. The association between type 1 diabetes and DRB1*03:01:01 was affected by DRB3*01:01:02... (More)
The possible contribution of HLA-DRB3, -DRB4 and -DRB5 alleles to type 1 diabetes risk and to autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A) or ZnT8 against either of the three amino acid variants, R, W or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next generation sequencing (NGS) was therefore used to determine all DRB alleles in consecutively diagnosed, islet autoantibody positive 1-18 years old type 1 diabetes patients (n=970) and controls (n=448). It was tested whether DRB3, DRB4 or DRB5 alleles were associated with the risk of DRB1 for autoantibodies, type 1 diabetes, or both. The association between type 1 diabetes and DRB1*03:01:01 was affected by DRB3*01:01:02 and DRB3*02:02:01. These DRB3 alleles were associated positively with GADA but negatively with ZnT8WA, IA-2A and IAA. The negative association between type 1 diabetes and DRB1*13:01:01 was affected by DRB3*01:01:02 to increase the risk and by DRB3*02:02:01 to maintain a negative association. DRB4*01:03:01 was strongly associated with type 1 diabetes (p=10(-36)) yet its association was extensively affected by DRB1 alleles from protective (DRB1*04:03:01) to high (DRB1*04:01:01) risk but with DRB1:04:05:01 it decreased the risk. HLA-DRB3, -DRB4, and -DRB5 affect type 1 diabetes risk and islet autoantibodies. HLA typing with next generation sequencing should prove useful to select participants for prevention or intervention trials. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
65
issue
3
pages
710 - 718
publisher
American Diabetes Association
external identifiers
  • pmid:26740600
  • wos:000370961000024
  • scopus:84962440475
ISSN
1939-327X
DOI
10.2337/db15-1115
language
English
LU publication?
yes
id
4e06c677-abf9-483d-956b-75a59056612e (old id 8592845)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26740600?dopt=Abstract
date added to LUP
2016-02-01 21:55:03
date last changed
2017-04-16 04:24:12
@article{4e06c677-abf9-483d-956b-75a59056612e,
  abstract     = {The possible contribution of HLA-DRB3, -DRB4 and -DRB5 alleles to type 1 diabetes risk and to autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A) or ZnT8 against either of the three amino acid variants, R, W or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next generation sequencing (NGS) was therefore used to determine all DRB alleles in consecutively diagnosed, islet autoantibody positive 1-18 years old type 1 diabetes patients (n=970) and controls (n=448). It was tested whether DRB3, DRB4 or DRB5 alleles were associated with the risk of DRB1 for autoantibodies, type 1 diabetes, or both. The association between type 1 diabetes and DRB1*03:01:01 was affected by DRB3*01:01:02 and DRB3*02:02:01. These DRB3 alleles were associated positively with GADA but negatively with ZnT8WA, IA-2A and IAA. The negative association between type 1 diabetes and DRB1*13:01:01 was affected by DRB3*01:01:02 to increase the risk and by DRB3*02:02:01 to maintain a negative association. DRB4*01:03:01 was strongly associated with type 1 diabetes (p=10(-36)) yet its association was extensively affected by DRB1 alleles from protective (DRB1*04:03:01) to high (DRB1*04:01:01) risk but with DRB1:04:05:01 it decreased the risk. HLA-DRB3, -DRB4, and -DRB5 affect type 1 diabetes risk and islet autoantibodies. HLA typing with next generation sequencing should prove useful to select participants for prevention or intervention trials.},
  author       = {Zhao, Lue Ping and Alshiekh, Shehab and Carlsson, Annelie and Larsson, Helena and Forsander, Gun and Ivarsson, Sten and Ludvigsson, Johnny and Kockum, Ingrid and Marcus, Claude and Persson, Martina and Samuelsson, Ulf and Örtqvist, Eva and Pyo, Chul-Woo and Nelson, Wyatt C and Geraghty, Daniel E and Lernmark, Åke},
  issn         = {1939-327X},
  language     = {eng},
  month        = {01},
  number       = {3},
  pages        = {710--718},
  publisher    = {American Diabetes Association},
  series       = {Diabetes},
  title        = {Next generation sequencing reveals that HLA-DRB3, -DRB4 and -DRB5 may be associated with islet autoantibodies and risk for childhood type 1 diabetes.},
  url          = {http://dx.doi.org/10.2337/db15-1115},
  volume       = {65},
  year         = {2016},
}