Longitudinal Pattern of First-Phase Insulin Response Is Associated With Genetic Variants Outside the Class II HLA Region in Children With Multiple Autoantibodies

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Koskinen , M K , Mikk , M-L , Laine , A-P , Lempainen , J , Löyttyniemi , E , Vähäsalo , P , Hekkala , A , Härkönen , T , Kiviniemi , M , Simell , O , Knip , M , Veijola , R , Ilonen , J & Toppari , J 2020 , ' Longitudinal Pattern of First-Phase Insulin Response Is Associated With Genetic Variants Outside the Class II HLA Region in Children With Multiple Autoantibodies ' , Diabetes , vol. 69 , no. 1 , pp. 12-19 . https://doi.org/10.2337/db19-0329

Title: Longitudinal Pattern of First-Phase Insulin Response Is Associated With Genetic Variants Outside the Class II HLA Region in Children With Multiple Autoantibodies
Author: Koskinen, Maarit K.; Mikk, Mari-Liis; Laine, Antti-Pekka; Lempainen, Johanna; Löyttyniemi, Eliisa; Vähäsalo, Paula; Hekkala, Anne; Härkönen, Taina; Kiviniemi, Minna; Simell, Olli; Knip, Mikael; Veijola, Riitta; Ilonen, Jorma; Toppari, Jorma
Contributor organization: Staff Services
HUS Children and Adolescents
Research Programs Unit
Children's Hospital
CAMM - Research Program for Clinical and Molecular Metabolism
University of Helsinki
Faculty of Medicine
Date: 2020-01
Language: eng
Number of pages: 8
Belongs to series: Diabetes
ISSN: 0012-1797
DOI: https://doi.org/10.2337/db19-0329
URI: http://hdl.handle.net/10138/309708
Abstract: A declining first-phase insulin response (FPIR) is associated with positivity for multiple islet autoantibodies, irrespective of class II HLA DR-DQ genotype. We examined the associations of FPIR with genetic variants outside the HLA DR-DQ region in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study in children with and without multiple autoantibodies. Association between FPIR and class I alleles A*24 and B*39 and eight single nucleotide polymorphisms outside the HLA region were analyzed in 438 children who had one or more FPIR results available after seroconversion. Hierarchical linear mixed models were used to analyze repeated measurements of FPIR. In children with multiple autoantibodies, the change in FPIR over time was significantly different between those with various PTPN2 (rs45450798), FUT2 (rs601338), CTSH (rs3825932), and IKZF4 (rs1701704) genotypes in at least one of the models. In general, children carrying susceptibility alleles for type 1 diabetes experienced a more rapid decline in insulin secretion compared with children without susceptibility alleles. The presence of the class I HLA A*24 allele was also associated with a steeper decline of FPIR over time in children with multiple autoantibodies. Certain genetic variants outside the class II HLA region may have a significant impact on the longitudinal pattern of FPIR.
Subject: BETA-CELL FUNCTION
DIABETES-MELLITUS
TYPE-1
DISEASE
SUSCEPTIBILITY
PROGRESSION
POLYMORPHISM
CHILDHOOD
DIAGNOSIS
RISK
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion


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