Genetic analysis of pharmacogenomic VIP variants of ABCB1, VDR and TPMT genes in an ethnically isolated population from the North Caucasus living in Jordan.

BACKGROUND Differences in individual responses to the same medications remarkably differ among populations. A number of genes that play integral roles in drug responses have been designated as very important pharmacogenes (VIP), as they are responsible for differences in drug safety, efficacy, and adverse drug reactions among certain ethnic groups. Identifying the polymorphic distribution of VIP in a range of ethnic groups will be conducive to population-based personalized medicine. OBJECTIVE The aim of the current study is to identify the polymorphic distribution of VIP regarding the Chechen minority group from Jordan and compare their allele frequencies with other populations. METHOD A total of 131 unrelated Chechen individuals from Jordan were randomly recruited for blood collection. Identification of allelic and genotypic frequencies of eleven VIP variants within the genes of interest (ABCB1, VDR and TPMT) was carried out by means of the MassARRAY®System (iPLEX GOLD). RESULTS Within ABCB1, we found that the minor allele frequencies of the rs1128503 (A:0.43), rs2032582 (A: 0.43), rs1045642 (A: 0.43). For VDR, the minor allele frequencies of rs11568820 (T: 0.18), rs1540339 (T: 0.30), rs1544410 (T: 0.41), rs2228570 (T: 0.24), rs3782905 (C: 0.28) and rs7975232 (C: 0.45). Finally, the minor allele frequencies for the TPMT rs1142345 and rs1800460 polymorphisms were found to be (C: 0.02) and (T: 0.01), respectively. CONCLUSION Significant differences in allelic frequencies of eleven ABCB1, VDR and TPMT VIP variants were found between Jordanian Chechens and other populations. In our study, the most populations that are similar to Chechens are those from South Asian, European (Finnish) and European, including: Utah residents with Northern and Western European ancestry, Toscani in Italia, Mexican ancestry in Los Angeles and Circassian from Jordan. The level of similarity between Chechens and those populations means that they might have shared high levels of gene flow in the past. The results obtained in this study will contribute to the worldwide pharmacogenomic databases and provide valuable information for future studies and better individualized treatments.

[1]  Amjad Khan,et al.  The effect of Gender and ABCB1 Gene Polymorphism on the Pharmacokinetics of Azithromycin in Healthy Male and Female Pakistani Subjects. , 2020, Canadian journal of physiology and pharmacology.

[2]  L. AL-Eitan,et al.  Association of Multiple Sclerosis Phenotypes with Single Nucleotide Polymorphisms of IL7R, LAG3, and CD40 Genes in a Jordanian Population: A Genotype-Phenotype Study , 2020, Biomolecules.

[3]  J. Beijnen,et al.  OATP1A/1B, CYP3A, ABCB1, and ABCG2 limit oral availability of the NTRK inhibitor larotrectinib, while ABCB1 and ABCG2 also restrict its brain accumulation , 2020, British journal of pharmacology.

[4]  A. Sahebkar,et al.  Vitamin D receptor genetic polymorphisms and the risk of multiple sclerosis: A systematic review and meta-analysis , 2020, Steroids.

[5]  N. Abdo,et al.  The Impact of IL-6 and IL-10 Gene Polymorphisms in Diffuse Large B-Cell Lymphoma Risk and Overall Survival in an Arab Population: A Case-Control Study , 2020, Cancers.

[6]  L. AL-Eitan,et al.  Pharmacogenomic landscape of VIP genetic variants in Jordanian Arabs and comparison with worldwide populations. , 2020, Gene.

[7]  L. AL-Eitan,et al.  The Association of IL-1 and HRAS Gene Polymorphisms with Breast Cancer Susceptibility in a Jordanian Population of Arab Descent: A Genotype–Phenotype Study , 2020, Cancers.

[8]  L. AL-Eitan,et al.  Genetic Polymorphisms of Pharmacogenes among the Genetically Isolated Circassian Subpopulation from Jordan , 2020, Journal of personalized medicine.

[9]  F. Khademi,et al.  Vitamin D receptor ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), and TaqI (rs731236) gene polymorphisms and susceptibility to pulmonary tuberculosis in an Iranian population: A systematic review and meta-analysis. , 2019, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[10]  L. AL-Eitan,et al.  Role of Four ABC Transporter Genes in Pharmacogenetic Susceptibility to Breast Cancer in Jordanian Patients , 2019, Journal of oncology.

[11]  L. AL-Eitan,et al.  Genetic Polymorphisms of Pharmacogenomic VIP Variants in the Circassian Subpopulation from Jordan. , 2019, Current drug metabolism.

[12]  L. AL-Eitan,et al.  Effects of MTHFR and ABCC2 gene polymorphisms on antiepileptic drug responsiveness in Jordanian epileptic patients , 2019, Pharmacogenomics and personalized medicine.

[13]  L. AL-Eitan,et al.  Effects of GRM4, SCN2A and SCN3B polymorphisms on antiepileptic drugs responsiveness and epilepsy susceptibility , 2019, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[14]  L. AL-Eitan,et al.  Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels , 2019, Journal of personalized medicine.

[15]  L. AL-Eitan,et al.  Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease , 2019, Pharmacogenomics and personalized medicine.

[16]  L. AL-Eitan,et al.  Effects of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness during the stabilization phase of therapy , 2019, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[17]  L. AL-Eitan,et al.  Effects of coagulation factor VII polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and maintenance phases of warfarin therapy , 2019, Pharmacogenomics and personalized medicine.

[18]  L. AL-Eitan,et al.  Impact of CYP2C9 and VKORC1 Polymorphisms on Warfarin Sensitivity and Responsiveness in Jordanian Cardiovascular Patients during the Initiation Therapy , 2018, Genes.

[19]  Islam M Al-Dalalah,et al.  The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy , 2018, Journal of personalized medicine.

[20]  G. Patrinos,et al.  Variants in TPMT, ITPA, ABCC4 and ABCB1 Genes As Predictors of 6-mercaptopurine Induced Toxicity in Children with Acute Lymphoblastic Leukemia , 2018, Journal of medical biochemistry.

[21]  D. Ochoa,et al.  Effect of ABCB1 C3435T Polymorphism on Pharmacokinetics of Antipsychotics and Antidepressants , 2018, Basic & clinical pharmacology & toxicology.

[22]  L. AL-Eitan,et al.  Practical Challenges and Translational Issues in Pharmacogenomics and Personalized Medicine from 2010 Onwards , 2017 .

[23]  L. Kang,et al.  Genetic polymorphisms of pharmacogenomic VIP variants in the Mongol of Northwestern China , 2016, BMC Genetics.

[24]  B. Mittal,et al.  The effect of ABCB1 polymorphisms on the outcome of breast cancer treatment , 2016, Pharmacogenomics and personalized medicine.

[25]  L. Kang,et al.  The population genetics of pharmacogenomics VIP variants in the Sherpa population. , 2016, Drug metabolism and pharmacokinetics.

[26]  C. Prakash,et al.  Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions. , 2015, Nuclear receptor research.

[27]  James Y. Zou.  Analysis of protein-coding genetic variation in 60,706 humans , 2015, Nature.

[28]  L. Kang,et al.  Genetic polymorphisms in very important pharmacogenomic (VIP) variants in the Tibetan population. , 2015, Genetics and molecular research : GMR.

[29]  L. Kang,et al.  Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China. , 2015, International journal of clinical and experimental pathology.

[30]  Y. Zhang,et al.  Genetic polymorphisms of pharmacogenomic VIP variants in the Uygur population from northwestern China , 2015, BMC Genetics.

[31]  Laith Haddad.  Emergence of Pharmacogenomics in Academic Medicine and Public Health in Jordan: History, Present State and Prospects , 2015 .

[32]  Yali Cui,et al.  Genetic polymorphisms of VIP variants in the Tajik ethnic group of northwest China , 2014, BMC Genetics.

[33]  K. Radhakrishnan,et al.  Genetic Association Analysis of ATP Binding Cassette Protein Family Reveals a Novel Association of ABCB1 Genetic Variants with Epilepsy Risk, but Not with Drug-Resistance , 2014, PloS one.

[34]  U. Lang,et al.  Impact of Vitamin D Receptor VDR rs2228570 Polymorphism in Oldest Old , 2013, Kidney and Blood Pressure Research.

[35]  C. L. Ventola.  Role of pharmacogenomic biomarkers in predicting and improving drug response: part 1: the clinical significance of pharmacogenetic variants. , 2013, P & T : a peer-reviewed journal for formulary management.

[36]  R. Loo,et al.  Pharmacometabonomics and personalized medicine , 2013, Annals of clinical biochemistry.

[37]  R. Dajani,et al.  Prevalence of MTHFR C677T Single Nucleotide Polymorphism in Genetically Isolated Populations in Jordan , 2013, Biochemical Genetics.

[38]  G. Gervasini,et al.  Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia , 2012, Front. Gene..

[39]  R. Altman,et al.  Very important pharmacogene summary for VDR , 2012, Pharmacogenetics and genomics.

[40]  Despina Sanoudou,et al.  Clinical Applications of Pharmacogenetics , 2012 .

[41]  R. Altman,et al.  Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). , 2011, Pharmacogenetics and genomics.

[42]  R. Altman,et al.  Very important pharmacogene summary: thiopurine S-methyltransferase. , 2010, Pharmacogenetics and genomics.

[43]  J. Ott,et al.  ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence. , 2008, Human molecular genetics.

[44]  V. Daggett,et al.  Four human thiopurine s-methyltransferase alleles severely affect protein structure and dynamics. , 2008, Journal of molecular biology.

[45]  Russ B. Altman,et al.  PharmGKB: Understanding the Effects of Individual Genetic Variants , 2008, Drug metabolism reviews.

[46]  R B Altman,et al.  The Pharmacogenetics Research Network: From SNP Discovery to Clinical Drug Response , 2007, Clinical pharmacology and therapeutics.

[47]  N. Tajik,et al.  GENETIC POLYMORPHISMS OF CYTOCHROME P450 ENZYMES 2C9 AND 2C19 IN A HEALTHY IRANIAN POPULATION , 2007, Clinical and experimental pharmacology & physiology.

[48]  L. Jorde,et al.  Genetic variation, classification and 'race' , 2004, Nature Genetics.

[49]  A. Uitterlinden,et al.  Genetics and biology of vitamin D receptor polymorphisms. , 2004, Gene.

[50]  Thierry Buclin,et al.  Polymorphisms in Human MDR1 (P‐glycoprotein): Recent Advances and Clinical Relevance , 2004, Clinical pharmacology and therapeutics.

[51]  Aravinda Chakravarti,et al.  Undetected genotyping errors cause apparent overtransmission of common alleles in the transmission/disequilibrium test. , 2003, American journal of human genetics.

[52]  Valentine J. Burroughs,et al.  Racial and ethnic differences in response to medicines: towards individualized pharmaceutical treatment. , 2002, Journal of the National Medical Association.

[53]  J. Markowitz,et al.  In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. , 2002, Life sciences.

[54]  E. Takeda,et al.  The Polymorphism in the Caudal‐Related Homeodomain Protein Cdx‐2 Binding Element in the Human Vitamin D Receptor Gene , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[55]  J. Harwood,et al.  Factors affecting levels of genetic diversity in natural populations. , 1998, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[56]  D. Meyers,et al.  Pharmacogenetics: implications of race and ethnicity on defining genetic profiles for personalized medicine. , 2014, The Journal of allergy and clinical immunology.

[57]  B. Shastry,et al.  Pharmacogenetics and the concept of individualized medicine , 2006, The Pharmacogenomics Journal.

[58]  J. Johnson,et al.  Pharmacogenomics: the inherited basis for interindividual differences in drug response. , 2001, Annual review of genomics and human genetics.