Genetic variants in the cytochrome P450 2D6 gene in the Sri Lankan population

Tharanga, T D Praveen; Jinadasa, C M V; Risama, M F; Galappatthy, Priyadarshani; Jayakody, R. L.; Dissanayake, Vajira H W

doi:10.4103/0971-6866.124361

Cited by 9 publications

(1 citation statement)

References 18 publications

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“… 25 In 2013, Tharanga et al detected the following alleles CYP2D6*3 (null functional), *10 (poorly functional), *2 (functional) and *4 (null functional) at the respective allele frequencies of 44.9%, 39.3%, 38.1% and 12.2%. 26 …”

Section: Introductionmentioning

confidence: 99%

<em>CYP2D6</em> polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study

Wickramage

Tennekoon

Ariyaratne

et al. 2017

BCTT

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Introduction and aimsTamoxifen is an adjuvant drug effective in treating hormone receptor – positive breast cancer. However, 30%–50% of patients relapse and many develop adverse effects, such as hot flashes and fatty liver. Allelic variations altering the activity of cytochrome P450-2D6 enzyme affect response to tamoxifen by modulating metabolism of tamoxifen into its pharmacologically active metabolite endoxifen. Although association between CYP2D6 polymorphisms and recurrence of breast cancer in patients on tamoxifen had been reported, little evidence exists on association between these polymorphisms and adverse effects to tamoxifen. This study explored the association between CYP2D6 polymorphisms and tamoxifen effects, hitherto not studied in Sri Lanka.MethodsA retrospective preliminary study was carried out on 24 breast cancer patients on tamoxifen for minimally 3 months attending National Cancer Institute, Maharagama, Sri Lanka. They were not on CYP2D6-inhibiting drugs, chemotherapy or other endocrine therapy, and had no conditions that could occur as adverse effects to tamoxifen before starting the therapy. Their blood samples were collected, DNA was extracted and genotyped using SNaPshot Multiplex sequencing based single-nucleotide polymorphism (SNP) assay.ResultsSNP/allele frequencies detected: 1846G>A (confirmatory of *4 null allele)=8.3%; 2549delA (confirmatory of *3 null allele)=50%; 100C>T (suggestive of *10 reduced functional allele, in addition to other alleles)=0%; combination of 2988G>A, −1584C and 2850C>T (strongly suggestive of *41 or other reduced functional allele)=4.8%. Occurrence of heterozygous 2988G>A SNP with −1584C and 2850C>T was significantly higher among those with ultrasound-diagnosed fatty liver following the commencement of tamoxifen therapy (P=0.029). Adverse effects occurred at a significantly higher frequency among postmenopausal women (P=0.041). Three patients who developed recurrence of breast cancer had no association with SNPs tested.ConclusionsCYP2D6 SNP combination 2988G>A, −1584C and 2850C>T, strongly suggestive of *41 reduced functional allele, is likely to be useful in predicting occurrence of adverse effect fatty liver in breast cancer patients on tamoxifen, thereby alternative treatment can be considered and lifestyle modifications implemented. Larger sample studies are recommended with the measurement of tamoxifen and metabolite levels. Alternative therapy should be considered for postmenopausal patients.

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Section: Introductionmentioning

confidence: 99%

<em>CYP2D6</em> polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study

Wickramage

Tennekoon

Ariyaratne

et al. 2017

BCTT

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Genetics and genomic medicine in Sri Lanka

Sirisena

Dissanayake

2019

Molec Gen & Gen Med

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The completion of the Human Genome Project in 2003 heralded in a new era marked by remarkable advances in biomedical research leading to the establishment of genomics‐based translational medicine mainly in the developed world. However, the development of such advances has been hampered in most parts of the developing world due to scarcity of resources and trained personnel. Genetics and genomic medicine are currently in the process of being integrated into the Sri Lankan health care system. These developments have taken place mainly due to the heightened awareness and increasing demands made by the public for provision of genetic diagnostic and therapeutic services in clinical care. Due to the exorbitant costs incurred in the maintenance of these services and the dearth of adequately trained manpower, only a few centers in the country, mainly in Universities or private sector, are currently engaged in providing these services to the public. This article aims to provide an overview of the genetics and genomic medicine services in Sri Lanka from its early developments to the current state.

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Effect of CYP2D6 genetic polymorphism on the metabolism of citalopram in vitro

Yuan

Fang

et al. 2016

Drug Metabolism and Pharmacokinetics

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Genetic variants in the cytochrome P450 2D6 gene in the Sri Lankan population

Cited by 9 publications

References 18 publications

<em>CYP2D6</em> polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study

<em>CYP2D6</em> polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study

Genetics and genomic medicine in Sri Lanka

Effect of CYP2D6 genetic polymorphism on the metabolism of citalopram in vitro

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