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Association of the WFS1 gene with disease progression in children with new onset T1D. Results from the Hvidoere study group on childhood diabetes

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@inproceedings{186a32cbb0734d1c9a05a4c4fbabd463,
title = "Association of the WFS1 gene with disease progression in children with new onset T1D. Results from the Hvidoere study group on childhood diabetes",
abstract = "Objective: The wolframin gene, WFS1, encodes a glucoprotein involved in the calcium homeostasis of the endoplasmatic reticulum; WFS1 is critical for the function and survival of the pancreatic beta-cells. Genetic variation within the WFS1 gene is known to be associated with T2D and for rare variants the Wolfram syndrome. The aim of this study was to investigate the impact of a common genetic variant (rs10010131) of the WFS1 gene on disease progression in a group of children newly diagnosed with T1D. Methods: The study is a multicenter longitudinal investigation with 18 participating paediatric centres from 15 countries. Clinical information and blood samples were collected from 275 children less than 16 years at diagnosis and at 1, 6, and 12 months after onset. Genotyping of the rs10010131 variant was done by KBioscience using an in-house KASPar assay system. Statistics: C-peptide, HbA1c, IDAA1c and proinsulin were analysed by multiple regression using age at onset, gender, DKA at onset, HLA class II risk groups, and genotypes as explanatory factors in a compound symmetric repeated measurement model. Results: The genotype frequencies were: 17{\%} (AA), 48{\%} (AG), 35{\%} (GG), where the G allele is the wildtype allele. In a dominant model the G allele carriers of the rs10010131 variant was significantly positively associated with stimulated C-peptide (est.: 1.73, P < 0.0001), negatively with HbA1c (est.: )0.49, P = 0.005), negatively with IDAA1c (est.: )0.67, P = 0.02) and positively with proinsulin (est.: 1.55, P = 0.005) the first 12 month after disease onset compared to the AA genotype carriers. Conclusions: A common variant of the WFS1 gene is highly associated with better residual beta-cell function and corresponding better metabolic control during disease progression in new onset T1D compared to AA genotype carriers. Thus, genotyping WFS1 might serve as a suitable selection tool for patients eligible for beta-cell regenerative intervention studies.",
author = "L.B. Nielsen and Andersen, {Marie Louise Max} and Jannete Svensson and Sven P{\"o}rksen and P Hougaard and Peter Swift and H Hoey and Mortensen, {Henrik Bindesb{\o}l} and Lars Hansen",
year = "2010",
language = "English",
journal = "Pediatric Diabetes",
issn = "1399-543X",
publisher = "Wiley",

}

RIS

TY - GEN

T1 - Association of the WFS1 gene with disease progression in children with new onset T1D. Results from the Hvidoere study group on childhood diabetes

AU - Nielsen, L.B.

AU - Andersen, Marie Louise Max

AU - Svensson, Jannete

AU - Pörksen, Sven

AU - Hougaard, P

AU - Swift, Peter

AU - Hoey, H

AU - Mortensen, Henrik Bindesbøl

AU - Hansen, Lars

PY - 2010

Y1 - 2010

N2 - Objective: The wolframin gene, WFS1, encodes a glucoprotein involved in the calcium homeostasis of the endoplasmatic reticulum; WFS1 is critical for the function and survival of the pancreatic beta-cells. Genetic variation within the WFS1 gene is known to be associated with T2D and for rare variants the Wolfram syndrome. The aim of this study was to investigate the impact of a common genetic variant (rs10010131) of the WFS1 gene on disease progression in a group of children newly diagnosed with T1D. Methods: The study is a multicenter longitudinal investigation with 18 participating paediatric centres from 15 countries. Clinical information and blood samples were collected from 275 children less than 16 years at diagnosis and at 1, 6, and 12 months after onset. Genotyping of the rs10010131 variant was done by KBioscience using an in-house KASPar assay system. Statistics: C-peptide, HbA1c, IDAA1c and proinsulin were analysed by multiple regression using age at onset, gender, DKA at onset, HLA class II risk groups, and genotypes as explanatory factors in a compound symmetric repeated measurement model. Results: The genotype frequencies were: 17% (AA), 48% (AG), 35% (GG), where the G allele is the wildtype allele. In a dominant model the G allele carriers of the rs10010131 variant was significantly positively associated with stimulated C-peptide (est.: 1.73, P < 0.0001), negatively with HbA1c (est.: )0.49, P = 0.005), negatively with IDAA1c (est.: )0.67, P = 0.02) and positively with proinsulin (est.: 1.55, P = 0.005) the first 12 month after disease onset compared to the AA genotype carriers. Conclusions: A common variant of the WFS1 gene is highly associated with better residual beta-cell function and corresponding better metabolic control during disease progression in new onset T1D compared to AA genotype carriers. Thus, genotyping WFS1 might serve as a suitable selection tool for patients eligible for beta-cell regenerative intervention studies.

AB - Objective: The wolframin gene, WFS1, encodes a glucoprotein involved in the calcium homeostasis of the endoplasmatic reticulum; WFS1 is critical for the function and survival of the pancreatic beta-cells. Genetic variation within the WFS1 gene is known to be associated with T2D and for rare variants the Wolfram syndrome. The aim of this study was to investigate the impact of a common genetic variant (rs10010131) of the WFS1 gene on disease progression in a group of children newly diagnosed with T1D. Methods: The study is a multicenter longitudinal investigation with 18 participating paediatric centres from 15 countries. Clinical information and blood samples were collected from 275 children less than 16 years at diagnosis and at 1, 6, and 12 months after onset. Genotyping of the rs10010131 variant was done by KBioscience using an in-house KASPar assay system. Statistics: C-peptide, HbA1c, IDAA1c and proinsulin were analysed by multiple regression using age at onset, gender, DKA at onset, HLA class II risk groups, and genotypes as explanatory factors in a compound symmetric repeated measurement model. Results: The genotype frequencies were: 17% (AA), 48% (AG), 35% (GG), where the G allele is the wildtype allele. In a dominant model the G allele carriers of the rs10010131 variant was significantly positively associated with stimulated C-peptide (est.: 1.73, P < 0.0001), negatively with HbA1c (est.: )0.49, P = 0.005), negatively with IDAA1c (est.: )0.67, P = 0.02) and positively with proinsulin (est.: 1.55, P = 0.005) the first 12 month after disease onset compared to the AA genotype carriers. Conclusions: A common variant of the WFS1 gene is highly associated with better residual beta-cell function and corresponding better metabolic control during disease progression in new onset T1D compared to AA genotype carriers. Thus, genotyping WFS1 might serve as a suitable selection tool for patients eligible for beta-cell regenerative intervention studies.

M3 - Conference article

JO - Pediatric Diabetes

JF - Pediatric Diabetes

SN - 1399-543X

ER -

ID: 32320942