Expression analysis of loci associated with type 2 diabetes in human tissues

C. Cotsapas; L. Prokunina-Olsson; C. Welch; R. Saxena; C. Weaver; N. Usher; C. Guiducci; S. Bonakdar; N. Turner; B. Lacroix; J. L. Hall

doi:10.1007/s00125-010-1861-2

Expression analysis of loci associated with type 2 diabetes in human tissues

C. Cotsapas, L. Prokunina-Olsson, C. Welch, R. Saxena, C. Weaver, N. Usher, C. Guiducci, S. Bonakdar, N. Turner, B. Lacroix, J. L. Hall

Medicine - Cardiology Division

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Abstract

Aims/hypothesis: Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues. Methods: We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n=50), colon (n=195) and liver (n=50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling. Results: Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver. Conclusions/ interpretation: This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.

Original language	English (US)
Pages (from-to)	2334-2339
Number of pages	6
Journal	Diabetologia
Volume	53
Issue number	11
DOIs	https://doi.org/10.1007/s00125-010-1861-2
State	Published - Nov 2010

Bibliographical note

Funding Information:
Acknowledgements We are grateful to S. Schmechel and S. Bowell for help with procurement of tissues from the University of Minnesota Tissue Procurement Facility. We would also like to thank M. Carlson for help in preparing samples for the analysis. The study was supported by an intramural research programme of NCI/NIH and by NIH grant 1R21DK078029-01 (to J. L. Hall).

Keywords

Colon
HHEX
IDE
Liver
Pancreas
SLC30A8
SNP
Type 2 diabetes
eQTL
mRNA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Expression analysis of loci associated with type 2 diabetes in human tissues",

abstract = "Aims/hypothesis: Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues. Methods: We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n=50), colon (n=195) and liver (n=50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling. Results: Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver. Conclusions/ interpretation: This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.",

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author = "C. Cotsapas and L. Prokunina-Olsson and C. Welch and R. Saxena and C. Weaver and N. Usher and C. Guiducci and S. Bonakdar and N. Turner and B. Lacroix and Hall, {J. L.}",

note = "Funding Information: Acknowledgements We are grateful to S. Schmechel and S. Bowell for help with procurement of tissues from the University of Minnesota Tissue Procurement Facility. We would also like to thank M. Carlson for help in preparing samples for the analysis. The study was supported by an intramural research programme of NCI/NIH and by NIH grant 1R21DK078029-01 (to J. L. Hall).",

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doi = "10.1007/s00125-010-1861-2",

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AU - Cotsapas, C.

AU - Prokunina-Olsson, L.

AU - Welch, C.

AU - Saxena, R.

AU - Weaver, C.

AU - Usher, N.

AU - Guiducci, C.

AU - Bonakdar, S.

AU - Turner, N.

AU - Lacroix, B.

AU - Hall, J. L.

N1 - Funding Information: Acknowledgements We are grateful to S. Schmechel and S. Bowell for help with procurement of tissues from the University of Minnesota Tissue Procurement Facility. We would also like to thank M. Carlson for help in preparing samples for the analysis. The study was supported by an intramural research programme of NCI/NIH and by NIH grant 1R21DK078029-01 (to J. L. Hall).

PY - 2010/11

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N2 - Aims/hypothesis: Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues. Methods: We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n=50), colon (n=195) and liver (n=50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling. Results: Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver. Conclusions/ interpretation: This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.

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KW - eQTL

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Expression analysis of loci associated with type 2 diabetes in human tissues

Abstract

Bibliographical note

Keywords

UN SDGs

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