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Variants in the FFAR1 Gene Are Associated with Beta Cell Function

Kalis, Martins; Levéen, Per LU ; Lyssenko, Valeriya LU ; Almgren, Peter LU ; Groop, Leif LU and Cilio, Corrado LU (2007) In PLoS One 2(11).
Abstract
BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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... (More)
BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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). CONCLUSIONS/SIGNIFICANCE: Variation in the FFAR1 gene may contribute to impaired beta cell function in T2D. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS One
volume
2
issue
11
publisher
Public Library of Science
external identifiers
  • PMID:17987108
  • WOS:000207459000002
  • Scopus:42549131357
ISSN
1932-6203
DOI
10.1371/journal.pone.0001090
language
English
LU publication?
yes
id
84403d0d-ebe4-4fe8-a777-89b02d1caca2 (old id 1137596)
date added to LUP
2008-04-30 10:00:52
date last changed
2016-10-13 04:26:58
@misc{84403d0d-ebe4-4fe8-a777-89b02d1caca2,
  abstract     = {BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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). CONCLUSIONS/SIGNIFICANCE: Variation in the FFAR1 gene may contribute to impaired beta cell function in T2D.},
  author       = {Kalis, Martins and Levéen, Per and Lyssenko, Valeriya and Almgren, Peter and Groop, Leif and Cilio, Corrado},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {ARRAY(0x7fb1198)},
  series       = {PLoS One},
  title        = {Variants in the FFAR1 Gene Are Associated with Beta Cell Function},
  url          = {http://dx.doi.org/10.1371/journal.pone.0001090},
  volume       = {2},
  year         = {2007},
}