HLA and non-HLA genes and familial predisposition to autoimmune diseases in families with a child affected by type 1 diabetes

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Parkkola , A , Laine , A-P , Karhunen , M , Härkönen , T , Ryhänen , S J , Ilonen , J , Knip , M & Finnish Pediat Diabet Register 2017 , ' HLA and non-HLA genes and familial predisposition to autoimmune diseases in families with a child affected by type 1 diabetes ' , PLoS One , vol. 12 , no. 11 , 0188402 . https://doi.org/10.1371/journal.pone.0188402

Title: HLA and non-HLA genes and familial predisposition to autoimmune diseases in families with a child affected by type 1 diabetes
Author: Parkkola, Anna; Laine, Antti-Pekka; Karhunen, Markku; Härkönen, Taina; Ryhänen, Samppa J.; Ilonen, Jorma; Knip, Mikael; Finnish Pediat Diabet Register
Contributor: University of Helsinki, HUS Children and Adolescents
University of Helsinki, Department of Political and Economic Studies (2010-2017)
University of Helsinki, Diabetes and Obesity Research Program
University of Helsinki, Children's Hospital
University of Helsinki, Clinicum
Date: 2017-11-28
Language: eng
Number of pages: 17
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/229918
Abstract: Genetic predisposition could be assumed to be causing clustering of autoimmunity in individuals and families. We tested whether HLA and non-HLA loci associate with such clustering of autoimmunity. We included 1,745 children with type 1 diabetes from the Finnish Pediatric Diabetes Register. Data on personal or family history of autoimmune diseases were collected with a structured questionnaire and, for a subset, with a detailed search for celiac disease and autoimmune thyroid disease. Children with multiple autoimmune diseases or with multiple affected first-or second-degree relatives were identified. We analysed type 1 diabetes related HLA class II haplotypes and genotyped 41 single nucleotide polymorphisms (SNPs) outside the HLA region. The HLA-DR4-DQ8 haplotype was associated with having type 1 diabetes only whereas the HLA-DR3-DQ2 haplotype was more common in children with multiple autoimmune diseases. Children with multiple autoimmune diseases showed nominal association with RGS1 (rs2816316), and children coming from an autoimmune family with rs11711054 (CCR3-CCR5). In multivariate analyses, the overall effect of non-HLA SNPs on both phenotypes was evident, associations with RGS1 and CCR3-CCR5 region were confirmed and additional associations were implicated: NRP1, FUT2, and CD69 for children with multiple autoimmune diseases. In conclusion, HLA-DR3-DQ2 haplotype and some non-HLA SNPs contribute to the clustering of autoimmune diseases in children with type 1 diabetes and in their families.
Subject: GENOME-WIDE ASSOCIATION
JUVENILE IDIOPATHIC ARTHRITIS
SYSTEMIC-LUPUS-ERYTHEMATOSUS
PRIMARY SCLEROSING CHOLANGITIS
INFLAMMATORY-BOWEL-DISEASE
SUSCEPTIBILITY LOCI
RISK LOCI
RHEUMATOID-ARTHRITIS
CELIAC-DISEASE
GENERALIZED VITILIGO
3111 Biomedicine
3123 Gynaecology and paediatrics
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