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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Aldehyde dehydrogenase ; chlorpropamide alcohol flushing test ; diabetes mellitus ; diabetic retinopathy ; ALDH2.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the influence of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) genotype on the clinical features of diabetes, 212 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) (154 males and 58 females aged 17–83 years; mean age 58.2 years) were investigated. Genotyping of ALDH2 was performed by the polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) method. The pattern of inheritance of diabetes and various clinical parameters was compared between active and inactive ALDH2 groups. Of the 212 subjects, 120 had active ALDH2 and 92 had inactive ALDH2. The percentage of patients with a diabetic mother was higher in the inactive ALDH2 group (32.6 %) than in the active ALDH2 group (19.2 %) (p 〈 0.05). The prevalence of proliferative retinopathy was lower in the inactive ALDH2 group than in the active ALDH2 group (p 〈 0.05). However, other clinical parameters showed no difference. We conclude that maternal inheritance of diabetes was common in the inactive ALDH2 group. The finding is suggestive of a relationship between alcohol intolerance and inheritance of diabetes. We speculate that the interaction between mitochondrial DNA and ALDH2 inactivity causes an increase of mitochondrial DNA mutations or deletions, thereby inducing the maternal inheritance of diabetes. The relationship of the ALDH2 genotype with proliferative retinopathy is interesting, because it resembles that of chlorpropamide alcohol flushing with severe diabetic retinopathy. The interaction of aldehyde dehydrogenase isoenzymes might have an aetiological role, since aldehyde dehydrogenase 1 plays an important part in oxidation of retinal to retinoic acid. However, the number of affected patients with proliferative retinopathy was small, hence, our result should be considered as a preliminary finding. [Diabetologia (1996) 39: 1115–1118]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Aldehyde dehydrogenase ; chlorpropamide alcohol flushing test ; diabetes mellitus ; diabetic retinopathy ; ALDH2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the influence of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) genotype on the clinical features of diabetes, 212 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) (154 males and 58 females aged 17–83 years; mean age 58.2 years) were investigated. Genotyping of ALDH2 was performed by the polymerase chain reaction — restriction fragment length polymorphism (PCR-RFLP) method. The pattern of inheritance of diabetes and various clinical parameters was compared between active and inactive ALDH2 groups. Of the 212 subjects, 120 had active ALDH2 and 92 had inactive ALDH2. The percentage of patients with a diabetic mother was higher in the inactive ALDH2 group (32.6%) than in the active ALDH2 group (19.2%) (p〈0.05). The prevalence of proliferative retinopathy was lower in the inactive ALDH2 group than in the active ALDH2 group (p〈0.05). However, other clinical parameters showed no difference. We conclude that maternal inheritance of diabetes was common in the inactive ALDH2 group. The finding is suggestive of a relationship between alcohol intolerance and inheritance of diabetes. We speculate that the interaction between mitochondrial DNA and ALDH2 inactivity causes an increase of mitochondrial DNA mutations or deletions, thereby inducing the maternal inheritance of diabetes. The relationship of the ALDH2 genotype with proliferative retinopathy is interesting, because it resembles that of chlorpropamide alcohol flushing with severe diabetic retinopathy. The interaction of aldehyde dehydrogenase isoenzymes might have an aetiological role, since aldehyde dehydrogenase 1 plays an important part in oxidation of retinal to retinoic acid. However, the number of affected patients with proliferative retinopathy was small, hence, our result should be considered as a preliminary finding.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Inactive aldehyde dehydrogenase-2 (ALDH2) is a well-known biological deterrent of heavy drinking among Asians, although some individuals who have inactive ALDH2 do become alcoholics. Unknown biological mechanisms facilitating the development of the disease may operate in such a way that these individuals overcome adverse reactions, or they may lower the intensity of the reactions. To examine our hypothesis that ethanol-oxidizing isoenzymes have lower catalytic properties in some persons, we investigated polymorphisms of ethanol-oxidizing enzymes that may alter their catalytic activities, viz., alcohol dehydrogenase-2 (ADH2) and -3 (ADH3), and cytochrome P450 2E1 (CYTP2E1), among 80 Japanese alcoholics with inactive ALDH2, 575 alcoholics with active ALDH2, and 461 controls. Although higher ADH2*1 and ADH3*2 allele frequencies were observed in alcoholics than in controls, there was no significant difference in ADH2 and ADH3 genotypes between alcoholics with inactive ALDH2 and alcoholics with active ALDH2. The genotype distributions of CYTP2E1 did not differ among the three groups, indicating no allelic association of the c1/c2 polymorphism of CYTP2E1 with alcoholism. These results suggest that genetic variations in ethanol-oxidizing activities are involved in the development of the disease, but that these variations are not specific in alcoholics with inactive ALDH2, a group at genetically low risk for alcoholism.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 103 (1996), S. 1205-1210 
    ISSN: 1435-1463
    Keywords: α1-antichymotrypsin ; Alzheimer's disease ; apolipoprotein E ; gene polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary α1-Antichymotrypsin (ACT), a component of the senile plaque of the Alzheimer's disese (AD) brain, has a possible role as a molecular chaper-one in developing AD pathology. This study was a search for the possible association of the two structural polymorphisms of ACT, Ala15 → Thr and Met389 → Val in the Japanese population. In 101 AD patients, genotype and allele frequencies of the two polymorphisms did not differ from those of 104 age-matched healthy controls. However, in those subjects in which the apolipoprotein ɛ4 allele was absent, the frequency of the Ala15 homozygote was significantly higher in the AD patients than in controls. This suggests that the Ala15 homozygote state may be a susceptibility marker for AD, interacting with apolipoprotein E genotype.
    Type of Medium: Electronic Resource
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