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Biomedical subjects

D P Agarwal

Publications and source records attributed to D P Agarwal.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacogenetics of alcohol metabolism and alcoholism.

The pharmacogenetic differences among individuals in their capacity to metabolize ingested alcohol are possibly responsible for the large inter-individual and inter-ethnic variations observed in the outcome of alcohol use and misuse. Based on results of adoption, twin, and family studies it is now widely accepted that the vulnerability to alcoholism is determined by genetic factors as well as by environment. There is a constant search for biological markers and specific genes which could identify individuals genetically predisposed to alcohol abuse and alcoholism. Numerous 'candidate genes' for alcoholism have been suggested including the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both ADH and ALDH exhibit genetic heterogeneity. An atypical form of ADH (ADH2), which contains a variant beta 2 subunit instead of the usual beta 1 subunit, differs substantially from the usual form in its kinetic properties and is found more frequently among the Japanese, Chinese and other Mongoloid populations than in Caucasoids and Negroids. A widely prevalent genetic polymorphism has been observed for ALDH; about 50% of Japanese and Chinese livers possess an inactive ALDH (ALDH2 isozyme) whereas none of the Caucasian or Negroid populations show this isozyme abnormality. These metabolic polymorphisms seem to contribute to differences in the in vivo elimination rate of ethanol and acetaldehyde, and may explain differences in alcohol-related behaviour and its disease outcome. Taken together, Orientals who possess an atypical ALDH2 gene are more sensitive to acute responses to alcohol, tend to be discouraged from drinking alcohol, and consequently are at lower risk of developing alcohol-related disorders. However, more work is needed to support these findings. Recent advances in molecular genetics have made it possible to analyze directly the human genome. This may help in a better understanding of the complex genetic and environmental factors in alcohol abuse by providing prospects for identification of gene loci which may be responsible for predisposition to, and protection from, alcoholism.

Alcohol Dehydrogenase↗
PubMed1979

Alcohol metabolizing enzymes: studies of isozymes in human biopsies and cultured fibroblasts.

Rapid and sensitive micromethods for the study of alcohol dehydrogenase and adehyde dehydrogenase isozymes in skin extracts, cultured fibroblasts and other organs are presented. Possibilities for the application of these techniques to the study of interindividual variations in response to alcohol are discussed. While fibroblasts cultured from a skin biopsy from one Japanese individual revealed a heterodimer (ADH2 2-1) of alcohol dehydrogenase, skin extract from another Japanese showed a homodimer (ADH2 2-2). Up to four isozyme sets for aldehyde dehydrogenase (ALDH) were detected in various human organs and at least three sets were found in skin and fibroblasts extracts. Our preliminary data on liver, stomach, and skin indicate that ALDH is polymorphic and several loci are concerned in the determination of these isozyme sets.

Alcohol Oxidoreductases↗
PubMed1978

Isozyme variations in acetaldehyde dehydrogenase (e.c.1.2.1.3) in human tissues.

NAD-dependent acetaldehyde dehydrogenase (ALDH) of human tissues was investigated by electrophoresis and enzyme assay. ALDH is located mainly in the liver and kidney. The isozymes consist of at least six different components. Five different phenotypes were found in a total of 68 human liver and kidney specimens. It is likely that three isozyme sets are concerned in determining ALDH types. The distribution of various phenotypes of ALDH isozyme sets is presented.

Aldehyde Oxidoreductases↗
PubMed1978

Human liver alcohol dehydrogenase isoenzyme variations. Improved separation methods using prolonged high voltage starch-gel electrophoresis and isoelectric focusing.

Human liver alcohol dehydrogenase isozyme patterns were studied using prolonged high voltage starch-gel electrophoresis and gel-slab isoelectric focusing. Homo- and heterodimers of ADH2 locus were easily distinguished from each other. The gene frequencies of ADH2 2 and ADH2 3 in 46 random liver samples from Germany were found to be 0.044 and 0.424 respectively.

Alcohol Oxidoreductases↗
PubMed1978

A silent gene (C3-) producing partial deficiency of the third component of human complement.

A family is described with 3 members in 3 generations being heterozygous for the silent gene C3-: one girl, her mother and grandfather had half normal C3 levels and were apparently incompatible homozygous. No significant deviation in the total hemolytic complement activity, serum concentration of Bf and C4 component was found in the affected individuals.

Blood Group Antigens↗
PubMed1977

Activity of creatine kinase isoenzyme MB in serum and red cell acetylcholinesterase variants in patients with Duchenne muscular dystrophy.

Activity of creatine kinase isoenzyme MB in serum and variants of red cell acetylcholinesterase were determined in patients with Duchenne muscular dystrophy, in other forms of Dystrophy and in family members of Duchenne patients and healthy controls. Creatine kinase isoenzyme MB was observed only in all cases of DMD as well as variants of red cell acetylcholinesterase characterized by so-called inhibitor numbers. Carriers of Duchenne muscular dystrophy can be distinguished from Duchenne patients and healthy controls by estimation of Acetylcholinesterase variants.

Acetylcholinesterase↗
PubMed1977

Genetic studies in Ecuador: acetylator phenotypes, red cell enzyme and serum protein polymorphisms of Shuara Indians.

Population genetic studies of Shuara Indians in Ecuador are performed for GPT, AP, PGM1, Ak, EsD, 6-PGD, Hp, Gc, C3, Bg, ChE, Tf, Pi, Bf phenotypes, IgG, IgA, IgM, C3, C3-proactivator, C4 levels and acetylator phenotypes. Some systems having a polymorphism in many other populations showed a lack of some of those alleles in the population under study (C3, ChE, Tf, AK and almost absent 6-PGD, Bg, Bf).

Acetylation↗
PubMed1976

Genetic polymorphism of C3 and serum levels of immunoglobulins, C3, C4 components of complement and C3-proactivator in four different populations of Afghanistan.

The C3 phenotype distribution was studied in 4 different populations from Afghanistan. The gene frequencies of C3S allele were: Tajiks (0,8547), Pushtoons (0.8812), Hazaras (0.9036) and Osbeks (0.8530). These values were significantly higher than in European populations studied previously. No significant differences were found between the mean serum levels of C3, C4 and C3-proactivator among 4 population groups. A higher concentration of IgG, IgA and IgM was observed in Afghanistan sera than reported for Europeans.

Afghanistan↗
PubMed1976

A note on suxamethonium sensitivity and serum cholinesterase variants.

Sera from 21 cases of prolonged apnoea which showed normal phenotype (UU) on the basis of dibucaine and fluoride inhibition were re-examined by replacing the substrate benzoylcholine with succinylcholine (suxamethonium). 9 samples had normal enzyme activity but low dibucaine number (DN = less than 20) indicating the atypical variant; 6 sera showed no detectable enzyme activity. The remaining 6 samples had enzyme activity and DN comparable with healthy controls. The occurence of new variants of serum cholinesterase sensitive only to succinylcholine is suggested.

Apnea↗
PubMed1975

Studies on the polymorphism of C3, Tf and Bg in Down's syndrome and other diseases.

The distribution of phenotypes C3, Ff and Bg was investigated in sera of patients with Down's syndrome, oligophrenia, Wilson's disease and heart infarct. Quantitative determination of the concentration of C3 and C4 components of human complement was also carried out in these patients. The results are compared to healthy controls and are discussed with already reported data from other authors. Despite differences in the percentage distribution of various phenotypes in the patients' sera as compared to that of the controls, no statistically significant association could be established.

Complement C3↗