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Unique splicing pattern of the TCF7L2 gene in human pancreatic islets.

Osmark, Peter LU ; Hansson, Ola LU orcid ; Jonsson, Anna LU ; Rönn, Tina LU ; Groop, Leif LU and Renström, Erik LU (2009) In Diabetologia 52. p.850-854
Abstract
AIMS/HYPOTHESIS: Intronic variation in the TCF7L2 gene exhibits the strongest association to type 2 diabetes observed to date, but the mechanism whereby this genetic variation translates into altered biological function is largely unknown. A possible explanation is a genotype-dependent difference in the complex splicing pattern; however, this has not previously been characterised in pancreatic or insulin target tissues. Here, the detailed TCF7L2 splicing pattern in five human tissues is described and dependence on risk genotype explored. METHODS: RT-PCR and quantitative real-time PCR were employed to characterise TCF7L2 splicing in pancreatic islets, blood lymphocytes, skeletal muscle and subcutaneous and visceral adipose tissue from... (More)
AIMS/HYPOTHESIS: Intronic variation in the TCF7L2 gene exhibits the strongest association to type 2 diabetes observed to date, but the mechanism whereby this genetic variation translates into altered biological function is largely unknown. A possible explanation is a genotype-dependent difference in the complex splicing pattern; however, this has not previously been characterised in pancreatic or insulin target tissues. Here, the detailed TCF7L2 splicing pattern in five human tissues is described and dependence on risk genotype explored. METHODS: RT-PCR and quantitative real-time PCR were employed to characterise TCF7L2 splicing in pancreatic islets, blood lymphocytes, skeletal muscle and subcutaneous and visceral adipose tissue from non-diabetic individuals. RESULTS: The mapping of TCF7L2 splice variants shows a specific pattern in pancreatic islets, with four predominant transcripts and high usage of the variable exons 4 and 15. The overall concentration of TCF7L2 mRNA is highest in islets and fat and lower in blood and muscle. No significant difference in overall amount or splicing pattern was observed between carriers and non-carriers of the rs7903146 risk (T) allele. However, incorporation of exon 4 in islets correlates positively with plasma HbA(1c) levels (r = 0.758; p = 0.018). CONCLUSIONS/INTERPRETATION: There were pronounced tissue-specific differences in the splicing of TCF7L2 with forms containing exon 4 and 15 being most abundant in islets. The incorporation of exon 4 in islets correlated with HbA(1c) levels. Further experiments will be needed to determine the direction of this correlation, and larger cohorts needed to unequivocally resolve whether there is a relationship between genotype and splicing in islets. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetologia
volume
52
pages
850 - 854
publisher
Springer
external identifiers
  • wos:000264884100017
  • pmid:19247628
  • scopus:64149124055
  • pmid:19247628
ISSN
1432-0428
DOI
10.1007/s00125-009-1293-z
language
English
LU publication?
yes
id
cfcad012-a53f-4ea5-8194-d15f30879bf4 (old id 1302046)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19247628?dopt=Abstract
date added to LUP
2016-04-04 07:42:40
date last changed
2025-04-04 14:26:51
@article{cfcad012-a53f-4ea5-8194-d15f30879bf4,
  abstract     = {{AIMS/HYPOTHESIS: Intronic variation in the TCF7L2 gene exhibits the strongest association to type 2 diabetes observed to date, but the mechanism whereby this genetic variation translates into altered biological function is largely unknown. A possible explanation is a genotype-dependent difference in the complex splicing pattern; however, this has not previously been characterised in pancreatic or insulin target tissues. Here, the detailed TCF7L2 splicing pattern in five human tissues is described and dependence on risk genotype explored. METHODS: RT-PCR and quantitative real-time PCR were employed to characterise TCF7L2 splicing in pancreatic islets, blood lymphocytes, skeletal muscle and subcutaneous and visceral adipose tissue from non-diabetic individuals. RESULTS: The mapping of TCF7L2 splice variants shows a specific pattern in pancreatic islets, with four predominant transcripts and high usage of the variable exons 4 and 15. The overall concentration of TCF7L2 mRNA is highest in islets and fat and lower in blood and muscle. No significant difference in overall amount or splicing pattern was observed between carriers and non-carriers of the rs7903146 risk (T) allele. However, incorporation of exon 4 in islets correlates positively with plasma HbA(1c) levels (r = 0.758; p = 0.018). CONCLUSIONS/INTERPRETATION: There were pronounced tissue-specific differences in the splicing of TCF7L2 with forms containing exon 4 and 15 being most abundant in islets. The incorporation of exon 4 in islets correlated with HbA(1c) levels. Further experiments will be needed to determine the direction of this correlation, and larger cohorts needed to unequivocally resolve whether there is a relationship between genotype and splicing in islets.}},
  author       = {{Osmark, Peter and Hansson, Ola and Jonsson, Anna and Rönn, Tina and Groop, Leif and Renström, Erik}},
  issn         = {{1432-0428}},
  language     = {{eng}},
  pages        = {{850--854}},
  publisher    = {{Springer}},
  series       = {{Diabetologia}},
  title        = {{Unique splicing pattern of the TCF7L2 gene in human pancreatic islets.}},
  url          = {{http://dx.doi.org/10.1007/s00125-009-1293-z}},
  doi          = {{10.1007/s00125-009-1293-z}},
  volume       = {{52}},
  year         = {{2009}},
}