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The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals

BACKGROUND: Variations within the FOXA family have been studied for a putative contribution to the risk of type 2 diabetes (T2D), and recently the minor T-allele of FOXA2 rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate...

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Autores principales: Banasik, Karina, Hollensted, Mette, Andersson, Ehm, Sparsø, Thomas, Sandbæk, Annelli, Lauritzen, Torsten, Jørgensen, Torben, Witte, Daniel R, Pedersen, Oluf, Hansen, Torben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344680/
https://www.ncbi.nlm.nih.gov/pubmed/22325233
http://dx.doi.org/10.1186/1471-2350-13-10
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author Banasik, Karina
Hollensted, Mette
Andersson, Ehm
Sparsø, Thomas
Sandbæk, Annelli
Lauritzen, Torsten
Jørgensen, Torben
Witte, Daniel R
Pedersen, Oluf
Hansen, Torben
author_facet Banasik, Karina
Hollensted, Mette
Andersson, Ehm
Sparsø, Thomas
Sandbæk, Annelli
Lauritzen, Torsten
Jørgensen, Torben
Witte, Daniel R
Pedersen, Oluf
Hansen, Torben
author_sort Banasik, Karina
collection PubMed
description BACKGROUND: Variations within the FOXA family have been studied for a putative contribution to the risk of type 2 diabetes (T2D), and recently the minor T-allele of FOXA2 rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate control procedure to enhance the statistical power of genome wide association studies in detecting associations between low-frequency variants and a given trait. Thus, the primary aim of this study was to investigate whether the minor T-allele of rs1205923 in FOXA2 associated with 1) decreased fasting plasma glucose and 2) a lower risk of developing T2D. Secondly, we investigated whether rs1205923 in FOXA2 associated with other glucose-related phenotypes. METHODS: The variant was genotyped in Danish individuals from four different study populations using KASPar(® )PCR SNP genotyping system. We examined for associations of the FOXA2 genotype with fasting plasma glucose and estimates of insulin release and insulin sensitivity following an oral glucose tolerance test in 6,162 Danish individuals from the population-based Inter99 study while association with T2D risk was assessed in 10,196 Danish individuals including four different study populations. RESULTS: The FOXA2 rs1209523 was not associated with fasting plasma glucose (effect size (β) = -0.03 mmol/l (95%CI: -0.07; 0.01), p = 0.2) in glucose-tolerant individuals from the general Danish population. Furthermore, when employing a case-control setting the variant showed no association with T2D (odds ratio (OR) = 0.82 (95%CI: 0.62-1.07), p = 0.1) among Danish individuals. However, when we performed the analysis in a subset of 6,022 non-obese individuals (BMI < 30 kg/m(2)) an association with T2D was observed (OR = 0.68 (95%CI: 0.49-0.94), p = 0.02). Also, several indices of insulin release and β-cell function were associated with the minor T-allele of FOXA2 rs1209523 in non-obese individuals. CONCLUSIONS: We failed to replicate association of the minor T-allele of FOXA2 rs1209523 with fasting plasma glucose in a population based sample of glucose tolerant individuals. More extensive studies are needed in order to fully elucidate the potential role of FOXA2 in glucose homeostasis.
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spelling pubmed-33446802012-05-05 The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals Banasik, Karina Hollensted, Mette Andersson, Ehm Sparsø, Thomas Sandbæk, Annelli Lauritzen, Torsten Jørgensen, Torben Witte, Daniel R Pedersen, Oluf Hansen, Torben BMC Med Genet Research Article BACKGROUND: Variations within the FOXA family have been studied for a putative contribution to the risk of type 2 diabetes (T2D), and recently the minor T-allele of FOXA2 rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate control procedure to enhance the statistical power of genome wide association studies in detecting associations between low-frequency variants and a given trait. Thus, the primary aim of this study was to investigate whether the minor T-allele of rs1205923 in FOXA2 associated with 1) decreased fasting plasma glucose and 2) a lower risk of developing T2D. Secondly, we investigated whether rs1205923 in FOXA2 associated with other glucose-related phenotypes. METHODS: The variant was genotyped in Danish individuals from four different study populations using KASPar(® )PCR SNP genotyping system. We examined for associations of the FOXA2 genotype with fasting plasma glucose and estimates of insulin release and insulin sensitivity following an oral glucose tolerance test in 6,162 Danish individuals from the population-based Inter99 study while association with T2D risk was assessed in 10,196 Danish individuals including four different study populations. RESULTS: The FOXA2 rs1209523 was not associated with fasting plasma glucose (effect size (β) = -0.03 mmol/l (95%CI: -0.07; 0.01), p = 0.2) in glucose-tolerant individuals from the general Danish population. Furthermore, when employing a case-control setting the variant showed no association with T2D (odds ratio (OR) = 0.82 (95%CI: 0.62-1.07), p = 0.1) among Danish individuals. However, when we performed the analysis in a subset of 6,022 non-obese individuals (BMI < 30 kg/m(2)) an association with T2D was observed (OR = 0.68 (95%CI: 0.49-0.94), p = 0.02). Also, several indices of insulin release and β-cell function were associated with the minor T-allele of FOXA2 rs1209523 in non-obese individuals. CONCLUSIONS: We failed to replicate association of the minor T-allele of FOXA2 rs1209523 with fasting plasma glucose in a population based sample of glucose tolerant individuals. More extensive studies are needed in order to fully elucidate the potential role of FOXA2 in glucose homeostasis. BioMed Central 2012-02-12 /pmc/articles/PMC3344680/ /pubmed/22325233 http://dx.doi.org/10.1186/1471-2350-13-10 Text en Copyright © 2012 Banasik et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Banasik, Karina
Hollensted, Mette
Andersson, Ehm
Sparsø, Thomas
Sandbæk, Annelli
Lauritzen, Torsten
Jørgensen, Torben
Witte, Daniel R
Pedersen, Oluf
Hansen, Torben
The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals
title The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals
title_full The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals
title_fullStr The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals
title_full_unstemmed The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals
title_short The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals
title_sort effect of foxa2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in danish individuals
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344680/
https://www.ncbi.nlm.nih.gov/pubmed/22325233
http://dx.doi.org/10.1186/1471-2350-13-10
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