Three most common nonsynonymous UGT1A6*2 polymorphisms (Thr181Ala, Arg184Serand Ser7Ala) and therapeutic response to deferiprone in β-thalassemia major patients

Dadheech, Sneha; Alapati, V. R.; Shaheen, Uzma; Hussien, Mohammed Dyia; Jain, Suman; Jyothy, A.; Munshi, Anjana

doi:10.1016/j.gene.2013.08.078

Cited by 11 publications

(9 citation statements)

References 20 publications

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“…In a study by Dadheech et al [13] , it was conducted to evaluate the association of UGT1A6 A541G, T19G and A552C SNPs with drug response and adverse drug reactions (ADRs) in β-thalassemia major patients receiving deferiprone therapy. While a significant difference in the genotypic distribution of the UGT1A6 Thr181Ala polymorphism has been observed in responders and non-responders, no difference was observed in the genotypic distribution between patients with and without ADR.…”

Section: Discussionmentioning

confidence: 99%

“…UGT1A6 c.541A>G, p.T181A, rs2070959 Analysis of the UGT1A6 c.541A>G SNP was performed using primers set; F: 5'-GGAAATACCTAGGAGCCCT GTGA-3' and R: 5'-AGGAGCCAAATGAGTGAGGGAG-3' . [13] The primers were used to amplify the 992 bp fragment of the gene. PCR products were digested at 37°C for 15 minutes using Fast Digest NsiI restriction enzyme (Thermo Fisher Scientific).…”

Section: Samplesmentioning

confidence: 99%

“…[9] In the UGT1A6 gene, the three most common nonsynonymous polymorphisms were Thr181Ala (541 A>G), Arg184Ser (552 A>C) and Ser7Ala (19 T>G). [13] Both Thr181Ala and Arg184Ser variants are mostly (>98%) in complete linkage disequilibrium. [14] These two variants result in a 30-50% decline in enzyme activity as opposed to the wild type allele.…”

Section: Introductionmentioning

confidence: 99%

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The Evaluation of Genetic Profiles of UGT1A4 and UGT1A6 in the Turkish Population

Şahinoğulları

2021

Journal of Contemporary Medicine

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Uridine diphosphate glucuronosyltransferases (UGTs) are a superfamily of conjugation phase II enzymes and is responsible for catalyzing the glucuronidation of many endobiotic or xenobiotic substrates. The present study aimed to determine allele and genotype frequencies of UGT1A4 c.142T>G, UGT1A6 c.541A>G and UGT1A6 c.19T>G polymorphisms in the healthy Turkish population and also to compare them with different population data.Material and Method: UGT1A4 c.142T>G, UGT1A6 c.541A>G and c.19T>G polymorphisms were determined in DNA samples of 114 healthy Turkish volunteers using polymerase chain reaction and restriction fragment length polymorphism methods. Results:The frequencies of variant alleles were 12.7% for UGT1A4 c.142T>G, 39.9% for UGT1A6 c.541A>G and 44.7% for UGT1A6 c.19T>G. The frequencies of the UGT1A4 and UGT1A6 variant alleles determined were observed to be similar to those of the majority of European populations. However, the UGT1A6 frequencies in the Turkish population differed significantly from those reported specifically for the Thai and East Asian populations. Conclusion:This study introduces the frequencies of UGT1A4 and UGT1A6 polymorphisms in the Turkish population. As a result of our literature reviews, this study is the first report that investigated the frequencies of UGT1A6 c.541A>G and c.19T>G polymorphisms in the healthy Turkish population. A study of the UGTA1A4*3 polymorphism was found in Turkish epilepsy patients in the literature search, but not in healthy individuals. Therefore, it can be stated that this study is also the first report investigating the UGT1A4*3 polymorphism in the healthy Turkish individuals. This study could ensure clinically beneficial information about drug metabolism by UGT1A4 and UGT1A6 in the Turkish population.

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Section: Discussionmentioning

confidence: 99%

Section: Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Evaluation of Genetic Profiles of UGT1A4 and UGT1A6 in the Turkish Population

Şahinoğulları

2021

Journal of Contemporary Medicine

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“…In relation to toxicity, the expression of the ABCB1 gene (also known as MDR1, encoding the P-glycoprotein) have studied, and an overexpression of MDR1 is the strongest predictive biomarker of taxanes (Paclitaxel and Docetaxel) resistance in general [257]. Pharmacogenetic studies of adverse drug response to Deferiprone found that the UGT1A6 2 Arg184Ser polymorphism of the UGT1A6 gene may interfere in adverse drug reactions (ADR), but not in drug resistance [259].…”

Section: Chelating Agentsmentioning

confidence: 99%

Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments

Sales

Prandi

Castro

et al. 2019

IJMS

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The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g. neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients’ quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs.

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“…Thus the affectivity of deferiprone may influenced by those genetic variants. It has been known that there are three most commonly known polymorphisms in UGT1A6 like Thr181Ala (541 A>G), Arg 184 Ser (552 A>C) and Ser 7Ala (19T>G); these are responsible for the efficacy of deferiprone treatment [23].…”

Section: Deferipronementioning

confidence: 99%

Pharmacogenomics of the Drugs used for the Treatment of Thalassemia

Panja¹,

Basu

2015

J Cytol Histol

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Thalassemia is one of the most prevalent inherited blood disorders all over the world. There are some specific hematologic tests and molecular genetic techniques known for diagnosis of thalassemia. Nowadays, various types of drugs are used for the treatment of thalassemia. Hydroxyurea, Hydroxycarbamide, Deferiprone, Deferisirox, Butyrate and its derivatives are some of the most common and well known drugs which are used for increasing the HbF percentage and iron chelation. Pharmacogenomics is the branch of pharmacology that is associated with the influence of genetic variations on the drug response among patients by correlating genetic variations, expression pattern or single-nucleotide polymorphisms with a drug's efficacy or toxicity. With the help of Pharmacogenomics study "personalized medicine" has been explored, in which drugs and drug combinations are optimized for the genetic makeup of each individual.

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Three most common nonsynonymous UGT1A6*2 polymorphisms (Thr181Ala, Arg184Serand Ser7Ala) and therapeutic response to deferiprone in β-thalassemia major patients

Cited by 11 publications

References 20 publications

The Evaluation of Genetic Profiles of UGT1A4 and UGT1A6 in the Turkish Population

The Evaluation of Genetic Profiles of UGT1A4 and UGT1A6 in the Turkish Population

Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments

Pharmacogenomics of the Drugs used for the Treatment of Thalassemia

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