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Current Drug Metabolism

Author(s): Laith Naser AL-Eitan*, Haneen Waleed Al-Maqableh, Namarg Nawwaf Mohammad, Nancy Mohamed Khair Hakooz and Rana Basem Dajani

DOI: 10.2174/1389200221666200505081139

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Genetic Analysis of Pharmacogenomic VIP Variants of ABCB1, VDR and TPMT Genes in an Ethnically Isolated Population from the North Caucasus Living in Jordan

Page: [307 - 317] Pages: 11

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Abstract

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.

Methods: 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, 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.

Keywords: Pharmacogenetics, VIP variants, Chechen, gene, pharmacogene, polymorphic distribution.

Graphical Abstract

[1]
Wang, L.; Aikemu, A.; Yibulayin, A.; Du, S.; Geng, T.; Wang, B.; Zhang, Y.; Jin, T.; Yang, J. Genetic polymorphisms of pharmacogenomic VIP variants in the Uygur population from northwestern China. BMC Genet., 2015, 16, 66-78.
[http://dx.doi.org/10.1186/s12863-015-0232-x] [PMID: 26091847]
[2]
Burroughs, V.J.; Maxey, R.W.; Levy, R.A. Racial and ethnic differences in response to medicines: towards individualized pharmaceutical treatment. J. Natl. Med. Assoc., 2002, 94(10)(Suppl.), 1-26.
[PMID: 12401060]
[3]
Wang, L.; Ren, Y.; Shi, X.; Yuan, D.; Liu, K.; Geng, T.; Li, G.; Kang, L.; Jin, T.B. The population genetics of pharmacogenomics VIP variants in the Sherpa population. Drug Metab. Pharmacokinet., 2016, 31(1), 82-89.
[http://dx.doi.org/10.1016/j.dmpk.2015.11.007] [PMID: 26825850]
[4]
Shastry, B.S. Pharmacogenetics and the concept of individualized medicine. Pharmacogenomics J., 2006, 6(1), 16-21.
[http://dx.doi.org/10.1038/sj.tpj.6500338] [PMID: 16302022]
[5]
Zhang, J.; Jin, T.; Yunus, Z.; Li, X.; Geng, T.; Wang, H.; Cui, Y.; Chen, C. Genetic polymorphisms of VIP variants in the Tajik ethnic group of northwest China. BMC Genet., 2014, 15, 102-110.
[http://dx.doi.org/10.1186/s12863-014-0102-y] [PMID: 25266489]
[6]
Jin, T.; Shi, X.; Wang, L.; Wang, H.; Feng, T.; Kang, L. Genetic polymorphisms of pharmacogenomic VIP variants in the Mongol of Northwestern China. BMC Genet., 2016, 17(1), 70-86.
[http://dx.doi.org/10.1186/s12863-016-0379-0] [PMID: 27233804]
[7]
Evans, W.E.; Johnson, J.A. Pharmacogenomics: the inherited basis for interindividual differences in drug response. Annu. Rev. Genomics Hum. Genet., 2001, 2, 9-39.
[http://dx.doi.org/10.1146/annurev.genom.2.1.9] [PMID: 11701642]
[8]
Sangkuhl, K.; Berlin, D.S.; Altman, R.B.; Klein, T.E. PharmGKB: understanding the effects of individual genetic variants. Drug Metab. Rev., 2008, 40(4), 539-551.
[http://dx.doi.org/10.1080/03602530802413338] [PMID: 18949600]
[9]
Giacomini, K.M.; Brett, C.M.; Altman, R.B.; Benowitz, N.L.; Dolan, M.E.; Flockhart, D.A.; Johnson, J.A.; Hayes, D.F.; Klein, T.; Krauss, R.M.; Kroetz, D.L.; McLeod, H.L.; Nguyen, A.T.; Ratain, M.J.; Relling, M.V.; Reus, V.; Roden, D.M.; Schaefer, C.A.; Shuldiner, A.R.; Skaar, T.; Tantisira, K.; Tyndale, R.F.; Wang, L.; Weinshilboum, R.M.; Weiss, S.T.; Zineh, I. Pharmacogenetics Research Network. The pharmacogenetics research network: from SNP discovery to clinical drug response. Clin. Pharmacol. Ther., 2007, 81(3), 328-345.
[http://dx.doi.org/10.1038/sj.clpt.6100087] [PMID: 17339863]
[10]
Jin, T.B.; Xun, X.J.; Shi, X.G.; Yuan, D.Y.; Feng, T.; Geng, T.T.; Kang, L.L. Genetic polymorphisms in very important pharmacogenomic (VIP) variants in the Tibetan population. Genet. Mol. Res., 2015, 14(4), 12497-12504.
[http://dx.doi.org/10.4238/2015.October.16.17] [PMID: 26505400]
[11]
Ortega, V.E.; Meyers, D.A. Pharmacogenetics: implications of race and ethnicity on defining genetic profiles for personalized medicine. J. Allergy Clin. Immunol., 2014, 133(1), 16-26.
[http://dx.doi.org/10.1016/j.jaci.2013.10.040] [PMID: 24369795]
[12]
He, Y.; Yang, H.; Geng, T.; Feng, T.; Yuan, D.; Kang, L.; Luo, M.; Jin, T. Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China. Int. J. Clin. Exp. Pathol., 2015, 8(10), 13293-13303.
[PMID: 26722533]
[13]
Milosevic, G.; Kotur, N.; Krstovski, N.; Lazic, J.; Zukic, B.; Stankovic, B.; Janic, D.; Katsila, T.; Patrinos, G.P.; Pavlovic, S.; Dokmanovic, L. Variants in TPMT, ITPA, ABCC4 and ABCB1 genes as predictors of 6-mercaptopurine induced toxicity in children with acute lymphoblastic leukemia. J. Med. Biochem., 2018, 37(3), 320-327.
[http://dx.doi.org/10.1515/jomb-2017-0060] [PMID: 30598629]
[14]
Dajani, R.; Fathallah, R.; Arafat, A.; AbdulQader, M.E.; Hakooz, N.; Al-Motassem, Y.; El-Khateeb, M. Prevalence of MTHFR C677T single nucleotide polymorphism in genetically isolated populations in Jordan. Biochem. Genet., 2013, 51(9-10), 780-788.
[http://dx.doi.org/10.1007/s10528-013-9606-9] [PMID: 23749065]
[15]
Jaimoukha, A. The Chechens: A hand book, 1st ed; Routledge Curzon: London, New York, 2005.
[16]
Boulton, D.W.; DeVane, C.L.; Liston, H.L.; Markowitz, J.S. In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci., 2002, 71(2), 163-169.
[http://dx.doi.org/10.1016/S0024-3205(02)01680-6] [PMID: 12031686]
[17]
Marzolini, C.; Paus, E.; Buclin, T.; Kim, R.B. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin. Pharmacol. Ther., 2004, 75(1), 13-33.
[http://dx.doi.org/10.1016/j.clpt.2003.09.012] [PMID: 14749689]
[18]
Prakash, C.; Zuniga, B.; Song, C.S.; Jiang, S.; Cropper, J.; Park, S.; Chatterjee, B. Nuclear receptors in drug metabolism, drug response and drug interactions. Nucl. Receptor Res., 2015, 2, 101-178.
[http://dx.doi.org/10.11131/2015/101178] [PMID: 27478824]
[19]
Sanoudou, D. Clinical Applications of Pharmacogenetics, 1st ed; InTech: Croatia, 2012.
[http://dx.doi.org/10.5772/1277]
[20]
Everett, J.R.; Loo, R.L.; Pullen, F.S. Pharmacometabonomics and personalized medicine. Ann. Clin. Biochem., 2013, 50(Pt 6), 523-545.
[http://dx.doi.org/10.1177/0004563213497929] [PMID: 23888060]
[21]
Ventola, C.L. Role of pharmacogenomic biomarkers in predicting and improving drug response: part 1: the clinical significance of pharmacogenetic variants. P&T, 2013, 38(9), 545-560.
[PMID: 24273401]
[22]
Pharm, GKB . VIPs: Very Important Pharmacogenes. Available at:, https://www.pharmgkb.org/view/vips.jsp
[23]
Zand, N.; Tajik, N.; Moghaddam, A.S.; Milanian, I. Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Iranian population. Clin. Exp. Pharmacol. Physiol., 2007, 34(1-2), 102-105.
[http://dx.doi.org/10.1111/j.1440-1681.2007.04538.x] [PMID: 17201743]
[24]
Jorde, L.B.; Wooding, S.P. Genetic variation, classification and ‘race’. Nat. Genet., 2004, 36(11)(Suppl.), S28-S33.
[http://dx.doi.org/10.1038/ng1435] [PMID: 15508000]
[25]
Mitchell, A.A.; Cutler, D.J.; Chakravarti, A. Undetected genotyping errors cause apparent overtransmission of common alleles in the transmission/disequilibrium test. Am. J. Hum. Genet., 2003, 72(3), 598-610.
[http://dx.doi.org/10.1086/368203] [PMID: 12587097]
[26]
http://ib.berkeley.edu/courses/bio1b/evolutionspring2010/pdfs/Moritz4Notes
[27]
Lek, M.; Karczewski, K.J.; Minikel, E.V.; Samocha, K.E.; Banks, E.; Fennell, T.; O’Donnell-Luria, A.H.; Ware, J.S.; Hill, A.J.; Cummings, B.B.; Tukiainen, T.; Birnbaum, D.P.; Kosmicki, J.A.; Duncan, L.E.; Estrada, K.; Zhao, F.; Zou, J.; Pierce-Hoffman, E.; Berghout, J.; Cooper, D.N.; Deflaux, N.; DePristo, M.; Do, R.; Flannick, J.; Fromer, M.; Gauthier, L.; Goldstein, J.; Gupta, N.; Howrigan, D.; Kiezun, A.; Kurki, M.I.; Moonshine, A.L.; Natarajan, P.; Orozco, L.; Peloso, G.M.; Poplin, R.; Rivas, M.A.; Ruano-Rubio, V.; Rose, S.A.; Ruderfer, D.M.; Shakir, K.; Stenson, P.D.; Stevens, C.; Thomas, B.P.; Tiao, G.; Tusie-Luna, M.T.; Weisburd, B.; Won, H.H.; Yu, D.; Altshuler, D.M.; Ardissino, D.; Boehnke, M.; Danesh, J.; Donnelly, S.; Elosua, R.; Florez, J.C.; Gabriel, S.B.; Getz, G.; Glatt, S.J.; Hultman, C.M.; Kathiresan, S.; Laakso, M.; McCarroll, S.; McCarthy, M.I.; McGovern, D.; McPherson, R.; Neale, B.M.; Palotie, A.; Purcell, S.M.; Saleheen, D.; Scharf, J.M.; Sklar, P.; Sullivan, P.F.; Tuomilehto, J.; Tsuang, M.T.; Watkins, H.C.; Wilson, J.G.; Daly, M.J.; MacArthur, D.G. Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60,706 humans. Nature, 2016, 536(7616), 285-291.
[http://dx.doi.org/10.1038/nature19057] [PMID: 27535533]
[28]
Levran, O.; O’Hara, K.; Peles, E.; Li, D.; Barral, S.; Ray, B.; Borg, L.; Ott, J.; Adelson, M.; Kreek, M.J. ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence. Hum. Mol. Genet., 2008, 17(14), 2219-2227.
[http://dx.doi.org/10.1093/hmg/ddn122] [PMID: 18424454]
[29]
Tulsyan, S.; Mittal, R.D.; Mittal, B. The effect of ABCB1 polymorphisms on the outcome of breast cancer treatment. Pharm. Genomics Pers. Med., 2016, 9, 47-58.
[PMID: 27175090]
[30]
Hodges, L.M.; Markova, S.M.; Chinn, L.W.; Gow, J.M.; Kroetz, D.L.; Klein, T.E.; Altman, R.B. Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenet. Genomics, 2011, 21(3), 152-161.
[http://dx.doi.org/10.1097/FPC.0b013e3283385a1c] [PMID: 20216335]
[31]
Balan, S.; Bharathan, S.P.; Vellichiramal, N.N.; Sathyan, S.; Joseph, V.; Radhakrishnan, K.; Banerjee, M. 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. PLoS One, 2014, 9(2)e89253
[http://dx.doi.org/10.1371/journal.pone.0089253] [PMID: 24586633]
[32]
Nazir, S.; Adnan, K.; Gul, R.; Ali, G.; Saleha, S.; Khan, A. The effect of gender and ABCB1 gene polymorphism on the pharmacokinetics of azithromycin in healthy male and female Pakistani subjects. Can. J.Physiol. Pharmacol., 2020. [published online ahead of print, 2020 Mar 3].,
[http://dx.doi.org/10.1139/cjpp-2019-0569] [PMID: 32125889]
[33]
Wang, Y.; Sparidans, R.W.; Li, W.; Lebre, M.C.; Beijnen, J.H.; Schinkel, A.H. OATP1A/1B, CYP3A, ABCB1, and ABCG2 limit oral availability of NTRK inhibitor larotrectinib, while ABCB1 and ABCG2 also restrict its brain accumulation. Br. J. Pharmacol.,, 2020. [published online ahead of print, 2020 Feb 22]..
[http://dx.doi.org/10.1111/bph.15034] [PMID: 32087611]
[34]
Saiz-Rodríguez, M.; Belmonte, C.; Román, M.; Ochoa, D.; Jiang-Zheng, C.; Koller, D.; Mejía, G.; Zubiaur, P.; Wojnicz, A.; Abad-Santos, F. Effect of ABCB1 C3435T polymorphism on pharmacokinetics of antipsychotics and antidepressants. Basic Clin. Pharmacol. Toxicol., 2018, 123(4), 474-485.
[http://dx.doi.org/10.1111/bcpt.13031] [PMID: 29723928]
[35]
Uitterlinden, A.G.; Fang, Y.; Van Meurs, J.B.; Pols, H.A.; Van Leeuwen, J.P. Genetics and biology of vitamin D receptor polymorphisms. Gene, 2004, 338(2), 143-156.
[http://dx.doi.org/10.1016/j.gene.2004.05.014] [PMID: 15315818]
[36]
Arai, H.; Miyamoto, K.I.; Yoshida, M.; Yamamoto, H.; Taketani, Y.; Morita, K.; Kubota, M.; Yoshida, S.; Ikeda, M.; Watabe, F.; Kanemasa, Y.; Takeda, E. The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene. J. Bone Miner. Res., 2001, 16(7), 1256-1264.
[http://dx.doi.org/10.1359/jbmr.2001.16.7.1256] [PMID: 11450701]
[37]
Poon, A.H.; Gong, L.; Brasch-Andersen, C.; Litonjua, A.A.; Raby, B.A.; Hamid, Q.; Laprise, C.; Weiss, S.T.; Altman, R.B.; Klein, T.E. Very important pharmacogene summary for VDR. Pharmacogenet. Genomics, 2012, 22(10), 758-763.
[http://dx.doi.org/10.1097/FPC.0b013e328354455c] [PMID: 22588316]
[38]
Glocke, M.; Lang, F.; Schaeffeler, E.; Lang, T.; Schwab, M.; Lang, U.E. Impact of vitamin D receptor VDR rs2228570 polymorphism in oldest old. Kidney Blood Press. Res., 2013, 37(4-5), 311-322.
[http://dx.doi.org/10.1159/000350159] [PMID: 24060611]
[39]
Wang, L.; Pelleymounter, L.; Weinshilboum, R.; Johnson, J.A.; Hebert, J.M.; Altman, R.B.; Klein, T.E. Very important pharmacogene summary: thiopurine S-methyltransferase. Pharmacogenet. Genom.,, 2010, 20(6), 401-405.
[http://dx.doi.org/10.1097/FPC.0b013e3283352860] [PMID: 20154640]
[40]
Mohammadi, A.; Azarnezhad, A.; Khanbabaei, H.; Izadpanah, E.; Abdollahzadeh, R.; Barreto, G.E.; Sahebkar, A. Vitamin D receptor genetic polymorphisms and the risk of multiple sclerosis: a systematic review and meta-analysis. Steroids,, 2020,.158108615 [published online ahead of print, 2020 Feb 22]..
[http://dx.doi.org/10.1016/j.steroids.2020.108615] [PMID: 32097613]
[41]
Mohammadi, A.; Khanbabaei, H.; Nasiri-Kalmarzi, R.; Khademi, F.; Jafari, M.; Tajik, N. 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; Microbiol Immunol Infect, 2019. [Epub Ahead of Print]
[http://dx.doi.org/10.1016/j.jmii.2019.08.011]
[42]
Rutherford, K.; Daggett, V. Four human thiopurine s-methyltransferase alleles severely affect protein structure and dynamics. J. Mol. Biol., 2008, 379(4), 803-814.
[http://dx.doi.org/10.1016/j.jmb.2008.04.032] [PMID: 18482735]
[43]
Gervasini, G.; Vagace, J.M. Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia. Front. Genet., 2012, 3, 249.
[http://dx.doi.org/10.3389/fgene.2012.00249] [PMID: 23189085]
[44]
Amos, W.; Harwood, J. Factors affecting levels of genetic diversity in natural populations. Philos. Trans. R. Soc. Lond. B Biol. Sci., 1998, 353(1366), 177-186.
[http://dx.doi.org/10.1098/rstb.1998.0200] [PMID: 9533122]
[45]
http://johnhawks.net/explainer/genetics/measuring-difference-between-population
[46]
Al-Eitan, L.N.; Haddad, Y.A. Emergence of pharmacogenomics in academic medicine and public health in Jordan: history, present state and prospects. Curr. Pharmacogenomics Person. Med., 2014, 12, 167-175.
[http://dx.doi.org/10.2174/1875692113666150115221210]
[47]
Al-Eitan, L.N.; Tarkhan, A.H. Practical challenges and translational issues in pharmacogenomics and personalized medicine from 2010 onwards. Curr. Pharmacogenomics Person. Med., 2014, 14, 7-17.
[http://dx.doi.org/10.2174/1875692115666161215103842]
[48]
Al-Eitan, L.N.; Al-Dalalah, I.M.; Elshammari, A.K.; Khreisat, W.H.; Almasri, A.Y. The impact of potassium channel gene polymorphisms on antiepileptic drug responsiveness in Arab patients with epilepsy. J. Pers. Med., 2018, 8(4), 37.
[http://dx.doi.org/10.3390/jpm8040037] [PMID: 30441785]
[49]
Al-Eitan, L.N.; Almasri, A.Y.; Khasawneh, R.H. Impact of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation therapy. Genes (Basel), 2018, 9(12), 578.
[http://dx.doi.org/10.3390/genes9120578] [PMID: 30486437]
[50]
Al-Eitan, L.N.; Almasri, A.Y.; Al-Habahbeh, S.O. Effects of coagulation factor VII polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and maintenance phases of warfarin therapy. Pharm. Genomics Pers. Med., 2019, 12, 1-8.
[http://dx.doi.org/10.2147/PGPM.S189458] [PMID: 30679919]
[51]
Al-Eitan, L.N.; Almasri, A.Y.; Al-Habahbeh, S.O. Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease. Pharm. Genomics Pers. Med., 2019, 12, 15-22.
[http://dx.doi.org/10.2147/PGPM.S189838] [PMID: 30962704]
[52]
Al-Eitan, L.N.; Almomani, B.A.; Nassar, A.M.; Elsaqa, B.Z.; Saadeh, N.A. Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels. J. Pers. Med., 2019, 9(1), 17.
[http://dx.doi.org/10.3390/jpm9010017] [PMID: 30934600]
[53]
Al-Eitan, L.N.; Al-Dalalah, I.M.; Aljamal, H.A. Effects of GRM4, SCN2A and SCN3B polymorphisms on antiepileptic drugs responsiveness and epilepsy susceptibility. Saudi Pharm. J., 2019, 27(5), 731-737.
[http://dx.doi.org/10.1016/j.jsps.2019.04.009] [PMID: 31297029]
[54]
Al-Eitan, L.N.; Almasri, A.Y.; Khasawneh, R.H. Effects of CYP2C9 and VKORC1 polymorphisms on warfarin sensitivity and responsiveness during the stabilization phase of therapy. Saudi Pharm. J., 2019, 27(4), 484-490.
[http://dx.doi.org/10.1016/j.jsps.2019.01.011] [PMID: 31061616]
[55]
Al-Eitan, L.N.; Al-Dalalah, I.M.; Mustafa, M.M.; Alghamdi, M.A.; Elshammari, A.K.; Khreisat, W.H.; Aljamal, H.A. Effects of MTHFR and ABCC2 gene polymorphisms on antiepileptic drug responsiveness in Jordanian epileptic patients. Pharm. Genomics Pers. Med., 2019, 12, 87-95.
[http://dx.doi.org/10.2147/PGPM.S211490] [PMID: 31354331]
[56]
Al-Eitan, L.N.; Rababa’h, D.M.; Alghamdi, M.A.; Khasawneh, R.H. Role of Four ABC Transporter genes in pharmacogenetic susceptibility to breast cancer in Jordanian patients. J. Oncol., 2019, 2019,6425708.
[http://dx.doi.org/10.1155/2019/6425708] [PMID: 31391850]
[57]
Al-Eitan, L.N.; Mohammad, N.N.; Al-Maqableh, H.W.; Hakooz, N.M.; Dajani, R.B. Genetic polymorphisms of pharmacogenomic vip variants in the circassian subpopulation from Jordan. Curr. Drug Metab., 2019, 20(8), 674-681.
[http://dx.doi.org/10.2174/1389200220666190729124000] [PMID: 31362667]
[58]
Al-Eitan, L.N. Pharmacogenomic landscape of VIP genetic variants in Jordanian Arabs and comparison with worldwide populations. Gene, 2020, 737144408
[http://dx.doi.org/10.1016/j.gene.2020.144408] [PMID: 32007583]
[59]
Al-Khatib, S.M.; Abdo, N.; Al-Eitan, L.N.; Al-Mistarehi, A.H.; Zahran, D.J.; Kewan, T.Z. 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. Cancers (Basel), 2020, 12(2), 382.
[http://dx.doi.org/10.3390/cancers12020382] [PMID: 32046104]
[60]
Al-Eitan, L.N.; Al-Ahmad, B.H.; Almomani, F.A. The association of il-1 and hras gene polymorphisms with breast cancer susceptibility in a jordanian population of Arab descent: a genotype-phenotype study. Cancers (Basel), 2020, 12(2), 283.
[http://dx.doi.org/10.3390/cancers12020283] [PMID: 31979384]
[61]
Al-Eitan, L.; Qudah, M.A.; Qawasmeh, M.A. Association of multiple sclerosis phenotypes with single nucleotide polymorphisms of IL7R, LAG3, and CD40 genes in a Jordanian population: a genotype-phenotype study. Biomolecules, 2020, 10(3)E356
[http://dx.doi.org/10.3390/biom10030356] [PMID: 32111053]
[62]
Al-Eitan, L.N.; Rababa’h, D.M.; Hakooz, N.M.; Alghamdi, M.A.; Dajani, R.B. Genetic polymorphisms of pharmacogenes among the genetically isolated circassian subpopulation from Jordan. J. Pers. Med., 2020, 10(1)E2
[http://dx.doi.org/10.3390/jpm10010002] [PMID: 31935801]