ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes

Yoshihiko Suzuki, Matsuo Taniyama, Taro Muramatsu, Susumu Higuchi, Shigeo Ohta, Yoshihito Atsumi, Kempei Matsuoka

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In the history of diabetes, chlorpropamide alcohol flushing test (CPAF) was a big topic in the 1970s to 1980s. Alcohol tolerance after chlorpropamide has prognostic significance, with the intolerant group (CPAF-positive group) being less prone to develop vascular complication than the tolerant group (CPAF-negative group). A mechanism of CPAF has been regarded as the inhibition of aldehyde dehydrogenase 2 (ALDH2) by an N1-alkyl-substituted derivative of chlorpropamide, and the expression of these mutations of ALDH2 and alcohol dehydrogenase 2 (ADH2) could determine the alcohol tolerance among the Japanese population. Therefore, we hypothesized that expression of different ALDH2 and ADH2 polymorphisms may induce differences in vascular complications in diabetes and conducted two studies. The first study (study 1) was to determine the association of ALDH2/AHD2 polymorphism with diabetic complications. To know the association of ALDH2/AHD2 polymorphism with diabetic vasculopathy and neuropathy, a total of 158 patients with type 2 diabetes were divided into four groups on the basis of ALDH2 "activity" and ADH2 "superactivity. " The frequency of proteinuria and the percentage of proliferative retinopathy among the patients with retinopathy was higher in those with active ALDH2 and superactive ADH2. We speculated that protein kinase C isoforms up-regulated by 4-hydroxynonenal that was detoxified by ALDH2 and ADH2 may account for the long-term development of diabetic nephropathy and severe retinopathy. As for neuropathy, the frequency of symptomatic neuropathy was higher in patients with inactive ALDH2 and usual ADH2. We speculate that increased tissue levels of toxic aldehyde could result from inactive ALDH2 and usual ADH2 expression, which results in the increased level of reactive aldehyde in sensory neuron pathway, thereby causing symptomatic polyneuropathy.

Original languageEnglish
JournalAlcoholism: Clinical and Experimental Research
Volume28
Issue number8 SUPPL.
DOIs
Publication statusPublished - 2004 Aug

Fingerprint

Aldehyde Dehydrogenase
Alcohol Dehydrogenase
Medical problems
Polymorphism
Type 2 Diabetes Mellitus
Chlorpropamide
Alcohols
Diabetes Complications
Aldehydes
Blood Vessels
Polyneuropathies
Diabetic Neuropathies
Poisons
Diabetic Nephropathies
Sensory Receptor Cells
Proteinuria
Protein Kinase C
Neurons
Protein Isoforms
History

Keywords

  • Alcohol Dehydrogenase 2
  • Aldehyde Dehydrogenase 2
  • Diabetic Neuropathy
  • Diabetic Vasculopathy
  • Type 2 Diabetes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes. / Suzuki, Yoshihiko; Taniyama, Matsuo; Muramatsu, Taro; Higuchi, Susumu; Ohta, Shigeo; Atsumi, Yoshihito; Matsuoka, Kempei.

In: Alcoholism: Clinical and Experimental Research, Vol. 28, No. 8 SUPPL., 08.2004.

Research output: Contribution to journalArticle

Suzuki, Yoshihiko ; Taniyama, Matsuo ; Muramatsu, Taro ; Higuchi, Susumu ; Ohta, Shigeo ; Atsumi, Yoshihito ; Matsuoka, Kempei. / ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes. In: Alcoholism: Clinical and Experimental Research. 2004 ; Vol. 28, No. 8 SUPPL.
@article{2f399641e89843b4bda3838f91bd6ed1,
title = "ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes",
abstract = "In the history of diabetes, chlorpropamide alcohol flushing test (CPAF) was a big topic in the 1970s to 1980s. Alcohol tolerance after chlorpropamide has prognostic significance, with the intolerant group (CPAF-positive group) being less prone to develop vascular complication than the tolerant group (CPAF-negative group). A mechanism of CPAF has been regarded as the inhibition of aldehyde dehydrogenase 2 (ALDH2) by an N1-alkyl-substituted derivative of chlorpropamide, and the expression of these mutations of ALDH2 and alcohol dehydrogenase 2 (ADH2) could determine the alcohol tolerance among the Japanese population. Therefore, we hypothesized that expression of different ALDH2 and ADH2 polymorphisms may induce differences in vascular complications in diabetes and conducted two studies. The first study (study 1) was to determine the association of ALDH2/AHD2 polymorphism with diabetic complications. To know the association of ALDH2/AHD2 polymorphism with diabetic vasculopathy and neuropathy, a total of 158 patients with type 2 diabetes were divided into four groups on the basis of ALDH2 {"}activity{"} and ADH2 {"}superactivity. {"} The frequency of proteinuria and the percentage of proliferative retinopathy among the patients with retinopathy was higher in those with active ALDH2 and superactive ADH2. We speculated that protein kinase C isoforms up-regulated by 4-hydroxynonenal that was detoxified by ALDH2 and ADH2 may account for the long-term development of diabetic nephropathy and severe retinopathy. As for neuropathy, the frequency of symptomatic neuropathy was higher in patients with inactive ALDH2 and usual ADH2. We speculate that increased tissue levels of toxic aldehyde could result from inactive ALDH2 and usual ADH2 expression, which results in the increased level of reactive aldehyde in sensory neuron pathway, thereby causing symptomatic polyneuropathy.",
keywords = "Alcohol Dehydrogenase 2, Aldehyde Dehydrogenase 2, Diabetic Neuropathy, Diabetic Vasculopathy, Type 2 Diabetes",
author = "Yoshihiko Suzuki and Matsuo Taniyama and Taro Muramatsu and Susumu Higuchi and Shigeo Ohta and Yoshihito Atsumi and Kempei Matsuoka",
year = "2004",
month = "8",
doi = "10.1097/01.ALC.0000133583.44581.99",
language = "English",
volume = "28",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "8 SUPPL.",

}

TY - JOUR

T1 - ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes

AU - Suzuki, Yoshihiko

AU - Taniyama, Matsuo

AU - Muramatsu, Taro

AU - Higuchi, Susumu

AU - Ohta, Shigeo

AU - Atsumi, Yoshihito

AU - Matsuoka, Kempei

PY - 2004/8

Y1 - 2004/8

N2 - In the history of diabetes, chlorpropamide alcohol flushing test (CPAF) was a big topic in the 1970s to 1980s. Alcohol tolerance after chlorpropamide has prognostic significance, with the intolerant group (CPAF-positive group) being less prone to develop vascular complication than the tolerant group (CPAF-negative group). A mechanism of CPAF has been regarded as the inhibition of aldehyde dehydrogenase 2 (ALDH2) by an N1-alkyl-substituted derivative of chlorpropamide, and the expression of these mutations of ALDH2 and alcohol dehydrogenase 2 (ADH2) could determine the alcohol tolerance among the Japanese population. Therefore, we hypothesized that expression of different ALDH2 and ADH2 polymorphisms may induce differences in vascular complications in diabetes and conducted two studies. The first study (study 1) was to determine the association of ALDH2/AHD2 polymorphism with diabetic complications. To know the association of ALDH2/AHD2 polymorphism with diabetic vasculopathy and neuropathy, a total of 158 patients with type 2 diabetes were divided into four groups on the basis of ALDH2 "activity" and ADH2 "superactivity. " The frequency of proteinuria and the percentage of proliferative retinopathy among the patients with retinopathy was higher in those with active ALDH2 and superactive ADH2. We speculated that protein kinase C isoforms up-regulated by 4-hydroxynonenal that was detoxified by ALDH2 and ADH2 may account for the long-term development of diabetic nephropathy and severe retinopathy. As for neuropathy, the frequency of symptomatic neuropathy was higher in patients with inactive ALDH2 and usual ADH2. We speculate that increased tissue levels of toxic aldehyde could result from inactive ALDH2 and usual ADH2 expression, which results in the increased level of reactive aldehyde in sensory neuron pathway, thereby causing symptomatic polyneuropathy.

AB - In the history of diabetes, chlorpropamide alcohol flushing test (CPAF) was a big topic in the 1970s to 1980s. Alcohol tolerance after chlorpropamide has prognostic significance, with the intolerant group (CPAF-positive group) being less prone to develop vascular complication than the tolerant group (CPAF-negative group). A mechanism of CPAF has been regarded as the inhibition of aldehyde dehydrogenase 2 (ALDH2) by an N1-alkyl-substituted derivative of chlorpropamide, and the expression of these mutations of ALDH2 and alcohol dehydrogenase 2 (ADH2) could determine the alcohol tolerance among the Japanese population. Therefore, we hypothesized that expression of different ALDH2 and ADH2 polymorphisms may induce differences in vascular complications in diabetes and conducted two studies. The first study (study 1) was to determine the association of ALDH2/AHD2 polymorphism with diabetic complications. To know the association of ALDH2/AHD2 polymorphism with diabetic vasculopathy and neuropathy, a total of 158 patients with type 2 diabetes were divided into four groups on the basis of ALDH2 "activity" and ADH2 "superactivity. " The frequency of proteinuria and the percentage of proliferative retinopathy among the patients with retinopathy was higher in those with active ALDH2 and superactive ADH2. We speculated that protein kinase C isoforms up-regulated by 4-hydroxynonenal that was detoxified by ALDH2 and ADH2 may account for the long-term development of diabetic nephropathy and severe retinopathy. As for neuropathy, the frequency of symptomatic neuropathy was higher in patients with inactive ALDH2 and usual ADH2. We speculate that increased tissue levels of toxic aldehyde could result from inactive ALDH2 and usual ADH2 expression, which results in the increased level of reactive aldehyde in sensory neuron pathway, thereby causing symptomatic polyneuropathy.

KW - Alcohol Dehydrogenase 2

KW - Aldehyde Dehydrogenase 2

KW - Diabetic Neuropathy

KW - Diabetic Vasculopathy

KW - Type 2 Diabetes

UR - http://www.scopus.com/inward/record.url?scp=16644368086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16644368086&partnerID=8YFLogxK

U2 - 10.1097/01.ALC.0000133583.44581.99

DO - 10.1097/01.ALC.0000133583.44581.99

M3 - Article

VL - 28

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 8 SUPPL.

ER -