A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes

Shiro Maeda; Masa-aki Kobayashi; Shin-ichi Araki; Tetsuya Babazono; Barry I Freedman; Meredith A Bostrom; Jessica N Cooke; Masao Toyoda; Tomoya Umezono; Lise Tarnow; Torben Hansen; Peter Gaede; Anders Jorsal; Daniel P K Ng; Minoru Ikeda; Toru Yanagimoto; Tatsuhiko Tsunoda; Hiroyuki Unoki; Koichi Kawai; Masahito Imanishi; Daisuke Suzuki; Hyoung Doo Shin; Kyong Soo Park; Atsunori Kashiwagi; Yasuhiko Iwamoto; Kohei Kaku; Ryuzo Kawamori; Hans-Henrik Parving; Donald W Bowden; Oluf Pedersen; Yusuke Nakamura

doi:10.1371/journal.pgen.1000842

A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes

Shiro Maeda, Masa-aki Kobayashi, Shin-ichi Araki, Tetsuya Babazono, Barry I Freedman, Meredith A Bostrom, Jessica N Cooke, Masao Toyoda, Tomoya Umezono, Lise Tarnow, Torben Hansen, Peter Gaede, Anders Jorsal, Daniel P K Ng, Minoru Ikeda, Toru Yanagimoto, Tatsuhiko Tsunoda, Hiroyuki Unoki, Koichi Kawai, Masahito ImanishiDaisuke Suzuki, Hyoung Doo Shin, Kyong Soo Park, Atsunori Kashiwagi, Yasuhiko Iwamoto, Kohei Kaku, Ryuzo Kawamori, Hans-Henrik Parving, Donald W Bowden, Oluf Pedersen, Yusuke Nakamura

72 Citations (Scopus)

Abstract

It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4x10^-6, odds ratio = 1.61, 95% confidence interval [CI]: 1.33-1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35x10^-8, odds ratio = 1.61, 95% Cl: 1.35-1.91). Rs2268388 was also associated with type 2 diabetes-associated end-stage renal disease (ESRD) in European Americans (p = 661024, odds ratio = 1.61, 95% Cl: 1.22-2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes.

Original language	English
Journal	P L o S Genetics
Volume	6
Issue number	2
Pages (from-to)	e1000842
ISSN	1553-7390
DOIs	https://doi.org/10.1371/journal.pgen.1000842
Publication status	Published - Feb 2010

Keywords

Acetyl-CoA Carboxylase
Adult
Animals
Base Pairing
Base Sequence
Case-Control Studies
Cells, Cultured
Cohort Studies
DNA
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Epithelial Cells
Gene Expression Profiling
Gene Expression Regulation, Enzymologic
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Kidney Tubules, Proximal
Mice
Molecular Sequence Data
Polymorphism, Single Nucleotide
Proteinuria
Transcription, Genetic

UN SDGs

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

Access to Document

10.1371/journal.pgen.1000842

Cite this

Maeda, S., Kobayashi, M., Araki, S., Babazono, T., Freedman, B. I., Bostrom, M. A., Cooke, J. N., Toyoda, M., Umezono, T., Tarnow, L., Hansen, T., Gaede, P., Jorsal, A., Ng, D. P. K., Ikeda, M., Yanagimoto, T., Tsunoda, T., Unoki, H., Kawai, K., ... Nakamura, Y. (2010). A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes. P L o S Genetics, 6(2), e1000842. https://doi.org/10.1371/journal.pgen.1000842

Maeda, S, Kobayashi, M, Araki, S, Babazono, T, Freedman, BI, Bostrom, MA, Cooke, JN, Toyoda, M, Umezono, T, Tarnow, L, Hansen, T, Gaede, P, Jorsal, A, Ng, DPK, Ikeda, M, Yanagimoto, T, Tsunoda, T, Unoki, H, Kawai, K, Imanishi, M, Suzuki, D, Shin, HD, Park, KS, Kashiwagi, A, Iwamoto, Y, Kaku, K, Kawamori, R, Parving, H-H, Bowden, DW, Pedersen, O & Nakamura, Y 2010, 'A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes', P L o S Genetics, vol. 6, no. 2, pp. e1000842. https://doi.org/10.1371/journal.pgen.1000842

@article{3b53261729634cf69a38bed606dbc761,

title = "A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes",

abstract = "It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4x10-6, odds ratio = 1.61, 95% confidence interval [CI]: 1.33-1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35x10-8, odds ratio = 1.61, 95% Cl: 1.35-1.91). Rs2268388 was also associated with type 2 diabetes-associated end-stage renal disease (ESRD) in European Americans (p = 661024, odds ratio = 1.61, 95% Cl: 1.22-2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes.",

keywords = "Acetyl-CoA Carboxylase, Adult, Animals, Base Pairing, Base Sequence, Case-Control Studies, Cells, Cultured, Cohort Studies, DNA, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Epithelial Cells, Gene Expression Profiling, Gene Expression Regulation, Enzymologic, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney Tubules, Proximal, Mice, Molecular Sequence Data, Polymorphism, Single Nucleotide, Proteinuria, Transcription, Genetic",

author = "Shiro Maeda and Masa-aki Kobayashi and Shin-ichi Araki and Tetsuya Babazono and Freedman, {Barry I} and Bostrom, {Meredith A} and Cooke, {Jessica N} and Masao Toyoda and Tomoya Umezono and Lise Tarnow and Torben Hansen and Peter Gaede and Anders Jorsal and Ng, {Daniel P K} and Minoru Ikeda and Toru Yanagimoto and Tatsuhiko Tsunoda and Hiroyuki Unoki and Koichi Kawai and Masahito Imanishi and Daisuke Suzuki and Shin, {Hyoung Doo} and Park, {Kyong Soo} and Atsunori Kashiwagi and Yasuhiko Iwamoto and Kohei Kaku and Ryuzo Kawamori and Hans-Henrik Parving and Bowden, {Donald W} and Oluf Pedersen and Yusuke Nakamura",

year = "2010",

month = feb,

doi = "10.1371/journal.pgen.1000842",

language = "English",

volume = "6",

pages = "e1000842",

journal = "P L o S Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "2",

}

TY - JOUR

T1 - A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes

AU - Maeda, Shiro

AU - Kobayashi, Masa-aki

AU - Araki, Shin-ichi

AU - Babazono, Tetsuya

AU - Freedman, Barry I

AU - Bostrom, Meredith A

AU - Cooke, Jessica N

AU - Toyoda, Masao

AU - Umezono, Tomoya

AU - Tarnow, Lise

AU - Hansen, Torben

AU - Gaede, Peter

AU - Jorsal, Anders

AU - Ng, Daniel P K

AU - Ikeda, Minoru

AU - Yanagimoto, Toru

AU - Tsunoda, Tatsuhiko

AU - Unoki, Hiroyuki

AU - Kawai, Koichi

AU - Imanishi, Masahito

AU - Suzuki, Daisuke

AU - Shin, Hyoung Doo

AU - Park, Kyong Soo

AU - Kashiwagi, Atsunori

AU - Iwamoto, Yasuhiko

AU - Kaku, Kohei

AU - Kawamori, Ryuzo

AU - Parving, Hans-Henrik

AU - Bowden, Donald W

AU - Pedersen, Oluf

AU - Nakamura, Yusuke

PY - 2010/2

Y1 - 2010/2

N2 - It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4x10-6, odds ratio = 1.61, 95% confidence interval [CI]: 1.33-1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35x10-8, odds ratio = 1.61, 95% Cl: 1.35-1.91). Rs2268388 was also associated with type 2 diabetes-associated end-stage renal disease (ESRD) in European Americans (p = 661024, odds ratio = 1.61, 95% Cl: 1.22-2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes.

AB - It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4x10-6, odds ratio = 1.61, 95% confidence interval [CI]: 1.33-1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35x10-8, odds ratio = 1.61, 95% Cl: 1.35-1.91). Rs2268388 was also associated with type 2 diabetes-associated end-stage renal disease (ESRD) in European Americans (p = 661024, odds ratio = 1.61, 95% Cl: 1.22-2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes.

KW - Acetyl-CoA Carboxylase

KW - Adult

KW - Animals

KW - Base Pairing

KW - Base Sequence

KW - Case-Control Studies

KW - Cells, Cultured

KW - Cohort Studies

KW - DNA

KW - Diabetes Mellitus, Type 2

KW - Diabetic Nephropathies

KW - Epithelial Cells

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Enzymologic

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Kidney Tubules, Proximal

KW - Mice

KW - Molecular Sequence Data

KW - Polymorphism, Single Nucleotide

KW - Proteinuria

KW - Transcription, Genetic

U2 - 10.1371/journal.pgen.1000842

DO - 10.1371/journal.pgen.1000842

M3 - Journal article

C2 - 20168990

SN - 1553-7390

VL - 6

SP - e1000842

JO - P L o S Genetics

JF - P L o S Genetics

IS - 2

ER -

A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this