Variants in the FFAR1 gene are associated with beta cell function.

<h4>Background</h4>The FFAR1 receptor is expressed mainly in pancreatic beta cells and is activated by medium to long chain free fatty acids (FFAs), as well as by thiazolidinediones, resulting in elevated Ca(2+) concentrations and promotion of insulin secretion. These properties suggest...

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Autores principales:	Martins Kalis, Per Levéen, Valeriya Lyssenko, Peter Almgren, Leif Groop, Corrado M Cilio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe4f56f92d6d4bce9fca8e2accaf2c31
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spelling	oai:doaj.org-article:fe4f56f92d6d4bce9fca8e2accaf2c312021-11-25T06:10:33ZVariants in the FFAR1 gene are associated with beta cell function.1932-620310.1371/journal.pone.0001090https://doaj.org/article/fe4f56f92d6d4bce9fca8e2accaf2c312007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0001090https://doaj.org/toc/1932-6203<h4>Background</h4>The FFAR1 receptor is expressed mainly in pancreatic beta cells and is activated by medium to long chain free fatty acids (FFAs), as well as by thiazolidinediones, resulting in elevated Ca(2+) concentrations and promotion of insulin secretion. These properties suggest that FFAR1 could be a mediator of lipotoxicity and a potential candidate gene for Type 2 diabetes (T2D). We therefore investigated whether variations at the FFAR1 locus are associated with T2D and beta cell function.<h4>Methodology/principal findings</h4>We re-sequenced the FFAR1 region in 96 subjects (48 healthy and 48 T2D individuals) and found 13 single nucleotide polymorphisms (SNPs) 8 of which were not previously described. Two SNPs located in the upstream region of the FFAR1 gene (rs1978013 and rs1978014) were chosen and genotyped in 1929 patients with T2D and 1405 healthy control subjects. We observed an association of rs1978013 and rs1978014 with insulinogenic index in males (p = 0.024) and females (p = 0.032), respectively. After Bonferroni corrections, no association with T2D was found in the case-control material, however a haplotype consisting of the T-G alleles conferred protection against T2D (p = 0.0010).<h4>Conclusions/significance</h4>Variation in the FFAR1 gene may contribute to impaired beta cell function in T2D.Martins KalisPer LevéenValeriya LyssenkoPeter AlmgrenLeif GroopCorrado M CilioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 2, Iss 11, p e1090 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martins Kalis Per Levéen Valeriya Lyssenko Peter Almgren Leif Groop Corrado M Cilio Variants in the FFAR1 gene are associated with beta cell function.
description	<h4>Background</h4>The FFAR1 receptor is expressed mainly in pancreatic beta cells and is activated by medium to long chain free fatty acids (FFAs), as well as by thiazolidinediones, resulting in elevated Ca(2+) concentrations and promotion of insulin secretion. These properties suggest that FFAR1 could be a mediator of lipotoxicity and a potential candidate gene for Type 2 diabetes (T2D). We therefore investigated whether variations at the FFAR1 locus are associated with T2D and beta cell function.<h4>Methodology/principal findings</h4>We re-sequenced the FFAR1 region in 96 subjects (48 healthy and 48 T2D individuals) and found 13 single nucleotide polymorphisms (SNPs) 8 of which were not previously described. Two SNPs located in the upstream region of the FFAR1 gene (rs1978013 and rs1978014) were chosen and genotyped in 1929 patients with T2D and 1405 healthy control subjects. We observed an association of rs1978013 and rs1978014 with insulinogenic index in males (p = 0.024) and females (p = 0.032), respectively. After Bonferroni corrections, no association with T2D was found in the case-control material, however a haplotype consisting of the T-G alleles conferred protection against T2D (p = 0.0010).<h4>Conclusions/significance</h4>Variation in the FFAR1 gene may contribute to impaired beta cell function in T2D.
format	article
author	Martins Kalis Per Levéen Valeriya Lyssenko Peter Almgren Leif Groop Corrado M Cilio
author_facet	Martins Kalis Per Levéen Valeriya Lyssenko Peter Almgren Leif Groop Corrado M Cilio
author_sort	Martins Kalis
title	Variants in the FFAR1 gene are associated with beta cell function.
title_short	Variants in the FFAR1 gene are associated with beta cell function.
title_full	Variants in the FFAR1 gene are associated with beta cell function.
title_fullStr	Variants in the FFAR1 gene are associated with beta cell function.
title_full_unstemmed	Variants in the FFAR1 gene are associated with beta cell function.
title_sort	variants in the ffar1 gene are associated with beta cell function.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/fe4f56f92d6d4bce9fca8e2accaf2c31
work_keys_str_mv	AT martinskalis variantsintheffar1geneareassociatedwithbetacellfunction AT perleveen variantsintheffar1geneareassociatedwithbetacellfunction AT valeriyalyssenko variantsintheffar1geneareassociatedwithbetacellfunction AT peteralmgren variantsintheffar1geneareassociatedwithbetacellfunction AT leifgroop variantsintheffar1geneareassociatedwithbetacellfunction AT corradomcilio variantsintheffar1geneareassociatedwithbetacellfunction
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Variants in the FFAR1 gene are associated with beta cell function.

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