Acetylation phenotype status in a Bangladeshi population and its comparison with that of other Asian population data

Zaid, R. B.; Nargis, M.; Neelotpol, Sharmind; Hannan, J. M. A.; Islam, Saiful; Akhter, Rubeenah; Ali, Liaquat; Ar, Khan

doi:10.1002/bdd.403

Cited by 10 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acetylator phenotype is a useful predictor of fast and slow acetylators of drugs, and the population differences among fast and slow acetylators have been recognized. In a study of the Bangladesh population (Zaid et al, 2004), it was shown that approximately 67% of the patients (total, 517) fell in the category of fast acetylators of sulfadimidine.…”

Section: Discussionmentioning

confidence: 99%

“…Acetylation is a process of phase II conjugation of sulfonamide biotransformation. The genetic variation affects the clinical consequences of being a rapid or slow acetylator (Zaid et al, 2004). The consequences of PG variation in these enzymes include (1) altered kinetics of specific drug substrates, (2) drug-drug interactions resulting from altered kinetics and (3) idiosyncratic adverse drug reactions.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cotrimoxazole and neonatal kernicterus: a review

Thyagarajan

Deshpande

2013

Drug and Chemical Toxicology

View full text Add to dashboard Cite

Sulfamethoxazole (SMX) and trimethoprim (TMP) individually and a combination known as cotrimoxazole (SMX-TMP) are widely used for the treatment of protozoan and bacterial infections. SMX-TMP is also one of the widely used antibiotics administered orally in neonates, along with gentamicin injection, for treating pneumonia and sepsis by home-based healthcare providers in Asian countries. Although the use of this drug has successfully reduced neonate mortality, there is a concern for it causing neurotoxicity. Previous clinical studies with sulfisoxazole have demonstrated occurrence of kernicterus in neonates. This sulfonamide is thought to displace bilirubin from its albumin-binding sites in plasma leading to an elevation of plasma bilirubin, which crosses the blood-brain barrier, reaches central neurons to cause kernicterus. We performed an extensive review of clinical and animal studies with cotrimoxazole, which showed no reported incidences of kernicterus with SMX-TMP use in neonates. EndNote, BasicBiosis, Embase, PubMed and Toxline database searches were conducted using specific keywords yielding 74 full-length articles relevant to the review. This review has taken into account various factors, including the disease itself, direct effects of the drug and its metabolism through conjugation and acetylation through a thorough review of the literature to examine the potentials of SMX-TMP to cause kernicterus in neonates. SMX-TMP in oral doses administered to neonates for 7–10 days is unlikely to cause kernicterus. Also, this review recommends warranting the need of future studies using animal models and clinical studies in humans to address SMX-TMP toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cotrimoxazole and neonatal kernicterus: a review

Thyagarajan

Deshpande

2013

Drug and Chemical Toxicology

View full text Add to dashboard Cite

show abstract

“…17 Previous work by our laboratory 18 indicated a phenotypic predominance of 74.5% SA in Hmong in contrast to other select Asian populations of geographic proximity in which SA phenotypes range from 6% to 45%. [19][20][21][22][23][24] Consequently, confirming this phenotypic predominance and its basis by correlating metabolic phenotype with NAT2 genotype represents a necessary step before conducting planned epidemiologic studies in the Hmong.…”

mentioning

confidence: 99%

Discordance Between N‐acetyltransferase 2 Phenotype and Genotype in a Population of Hmong Subjects

Straka

Burkhardt

Lang

et al. 2006

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Polymorphisms of N-acetyltransferase 2 (NAT2) acetylation may influence drug toxicities and efficacy and are associated with a differential susceptibility to select cancers. Acetylation phenotype may have clinical implications. The purposes of this study were to determine the genetic basis of an apparent predominance of slow acetylation phenotype and to assess concordance with genotype in a population of Hmong residing in Minnesota. Urine and DNA obtained from unrelated Hmong 18 to 65 years of age were used to determine phenotype from caffeine metabolites, whereas direct nucleotide sequencing of the NAT2 coding region, followed by cloning, identified all known allelic variants. From 61 subjects (27 men, 30 +/- 11 years), analysis of 50 urine-DNA pairs identified 46 (92%) slow acetylators and 4 (8%) rapid acetylators by phenotype. Genotypic analysis inferred 5 (10%) slow acetylators and 45 (90%) rapid acetylators. There is 86% discordance between phenotype and genotype. A predominance of NAT2 slow acetylation phenotype in the Hmong is confirmed, and a significant discordance between NAT2 phenotype and genotype is identified. In this population, slow acetylation phenotype determined by a metabolic probe would not have been predicted by genotype alone. Environmental, genetic, or phenotypic anomalies that may contribute to this discordance should be considered and evaluated in future studies within this unique population.

show abstract

“…Twenty-eight polymorphic variants of the NAT2 gene have been found [12]. The distribution of NAT2 phenotypes has been demonstrated to be associated with geographical latitude [15], the frequency of the fast N-acetylation phenotypes increasing when moving to the equator.Arylalkyl N-acetyl transferase catalyzes the synthesis of melatonin from serotonin in the pineal gland. Melatonin regulates immunity; normalizes sleep; relieves depression; and possess antioxidant, sedative, antiproliferative, and protective properties.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

The Relationship between the NAT2 Phenotype Polymorphism and Predisposition to Suicide in Ethnic Populations

Radkevich

Gyul'azizova

Nikolaeva

et al. 2005

Dokl Biochem Biophys

View full text Add to dashboard Cite

Suicide is deliberate self-damage, often with a lethal outcome. The causes of suicidal behavior are multiple, complex, and largely unclear. Despite numerous studies on the social, biological, psychological, and psychiatric causes of suicide, as well as its gender, agerelated, and temporal characteristics [2][3][4][5], specific causes of suicide remain unknown. Suicide rates are increasing every year in connection with intense population aging and may become one of the leading causes of mortality in socially prosperous countries. However, suicides are distributed nonuniformly over the world. For example, suicides are considerably more frequent in Europe than in South America. This indicates that the etiology and pathogenesis of suicide behavior are unclear and require further studying.The mechanisms of individual predisposition to various diseases has become an urgent problem now, when the human genome is being deciphered [1,[6][7][8][11][12][13]. In the early 1980s, Academician L.A. Piruzyan enunciated the concept of personal "metabolic passport" for individualizing the prevention and chemotherapy of various diseases and decreasing side effects of drugs [6,7].The so-called "environmental" genes, i.e., the genes encoding xenobiotic detoxification enzymes, play an important role in the human metabolic passport. These are cytochrome P-450, NAT1, NAT2, GSTM1, and other enzymes whose forms largely vary due to genetic polymorphisms. The enzyme N-acetyl transferase (NAT2) belongs to the GNAT family; it is involved in the genetically determined biotransformation of exogenous (arylamines and heterocyclic compounds) and endogenous (lipids, hormones, neurotransmitters, immune factors, and inflammation factors) substrates and exhibits a bimodal distribution in human populations, dividing them into slow and fast N-acetylators according to the enzyme phenotype [11,12]. Neither of the N-acetylation phenotypes has been found to have a physiological advantage over the other. The numbers of fast and slow N-acetylators widely vary in different ethnic groups [6,7]. Twenty-eight polymorphic variants of the NAT2 gene have been found [12]. The distribution of NAT2 phenotypes has been demonstrated to be associated with geographical latitude [15], the frequency of the fast N-acetylation phenotypes increasing when moving to the equator.Arylalkyl N-acetyl transferase catalyzes the synthesis of melatonin from serotonin in the pineal gland. Melatonin regulates immunity; normalizes sleep; relieves depression; and possess antioxidant, sedative, antiproliferative, and protective properties. A decrease in melatonin synthesis in the pineal gland or disturbance of the rhythm of its secretion has been found in diabetes mellitus, depression, Alzheimer's diseases, Parkinson's disease, immunodeficiencies, and cancer [9,10,14]. The main function of the pineal gland is the regulation of circadian (daily) and circanual (seasonal) biorhythms, endocrine functions, metabolism, and adaptation to changing illumination. V. Pierpaoli considers the pineal gland ...

show abstract

Acetylation phenotype status in a Bangladeshi population and its comparison with that of other Asian population data

Cited by 10 publications

References 14 publications

Cotrimoxazole and neonatal kernicterus: a review

Cotrimoxazole and neonatal kernicterus: a review

Discordance Between N‐acetyltransferase 2 Phenotype and Genotype in a Population of Hmong Subjects

The Relationship between the NAT2 Phenotype Polymorphism and Predisposition to Suicide in Ethnic Populations

Contact Info

Product

Resources

About