Yıl: 2022 Cilt: 42 Sayı: 3 Sayfa Aralığı: 213 - 220 Metin Dili: İngilizce DOI: 10.5336/medsci.2021-87249 İndeks Tarihi: 27-10-2022

Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research

Öz:
Objective: In this study, the relationship between theMDR1 gene and ankylosing spondylitis (AS) was investigated. Genetic and envi- ronmental factors are known to play an important role in thepathogenesis of AS. It is obvious that different patients have different reactions to prescribed drugs and drug dosages during standard treatment. One of these factors is the P-glycoprotein encoded by the MDR1 gene. The most widely studied alleles of this gene are rs1045642-NM_000927.4:c.3435T>C, p. Ile1145Ile (C3435T), rs2032582-NM_000927.4:c.2677T>G/A, p. Ser893Ala/Thr (G2677T/A) and silent rs1128503-NM_000927.4:c.1236T>C, p. Gly412Gly (C1236T).Mate- rial and Methods: The study group was formed from 34 patients with bio- logical therapy, 32 patients with other treatments (66 AS patients in total) and 32 healthy individuals. DNA isolation was performed using a High Pure PCR Template Preparation Kit. RNA isolation was performed with TRIzol man- ual isolation. For quantitative real-time polymerase chain reaction, a Roche LightCycler FastStart DNA Master device HybProbe was used. Results: There was no statistically significant difference between groups regarding the investigated polymorphisms. In the biological therapy [tumor necrosis factor alpha (TNF-α) inhibitor] group, a significant decrease was found in MDR1 gene expression (p<0.001). Conclusion: In conclusion, we could say that there is no relation between single-nucleotide polymorphism and treatment choice and response for AS patients. Decreased MDR1 expres- sion can be explained by the possible downregulatory effect of TNF-α in- hibitors.
Anahtar Kelime:

MDR1 Geni ile Ankilozan Spondilit Arasındaki İlişkinin İncelenmesi: Olgu Kontrol Araştırması

Öz:
Bu çalışmada MDR1 geni ile Ankilozan spondilit araştırıldı. Genetik ve çevresel faktörlerin ankilozan spondilit (AS) patogenezinde önemli rol oynadığı bilinmektedir. Standart tedavi sırasında farklı hastala- rın, reçeteli ilaçlara ve ilaç dozajlarına karşı farklı tepkileri olduğu açıktır. Bu faktörlerden biri, MDR1 geni tarafından kodlanan P-glikoproteindir. Bu genin en çok çalışılan allelleri rs1045642-NM_0009 27.4:c.3435T>C, p. Ile1145Ile (C3435T), rs2032582- NM_ 000927. 4:c.2677T>G/A, p. Ser893Ala/Thr (G2677T/A) ve sessiz rs1128503-NM_000927.4:c.1236T>C, p. Gly412Gly (C1236T)’dir. Gereç ve Yöntemler: Otuz dört biyolojik tedavi, 32 di ğer te- davileri alan toplam 66 AS hastas ı ve 32 sağlıklı herhangi bir ilaç kullanma- yan bireyden olu şan grup kar şılaştırıldı. DNA izolasyonu High Pure PCR Template Preparation Kiti kullanılarak gerçekleştirildi. RNA izolasyonu tri- zolle yapıldı. Kantitatif gerçek zamanlı polimeraz zincir reaksiyonu, Roche LightCycler FastStart DNA Master HybProbe cihaz ında gerçekleştirildi. Bulgular: Çalışmamızın sonucunda, ara ştırılan polimorfizmlerle ilgili gruplar arasında istatistiksel olarak anlaml ı bir fark yoktu. Biyolojik te- davileri [tümör nekrozis faktör alfa (TNF- α)] kullanan AS grubunun, MDR1 gen ekspresyonu arasında anlamlı bir farklılık bulundu (p<0,001). Sonuç: Sonuç olarak AS hastalarında tek nükleotid polimorfizmi ile tedavi seçimi ve yanıt arasında bir ilişki olmadığını söyleyebiliriz. Azalan MDR1 ekspresyonu, TNF-α inhibitörlerinin olası baskılayıcı regülatör etkisi ile açıklanabilir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. pelechas E, Kaltsonoudis E, voulgari pv, Drosos AA. Illustrated Hand- book of Rheumatic and Musculo-Skeletal Diseases. 1st ed. Cham, Switzerland: Springer International publishing; 2019. [Crossref]
  • 2. Feldtkeller E, Khan MA, van der Heijde D, van der Linden S, Braun J. Age at disease onset and diagnosis delay in HLA-B27 negative vs. pos- itive patients with ankylosing spondylitis. Rheumatol Int. 2003;23(2):61- 6. [Crossref] [pubMed]
  • 3. Hoyle E, Laval SH, Calin A, Wordsworth Bp, Brown MA. The x-chromo- some and susceptibility to ankylosing spondylitis. Arthritis Rheum. 2000;43(6):1353-5. [Crossref] [pubMed]
  • 4. Sharip A, Kunz J. understanding the pathogenesis of spondyloarthritis. Biomolecules. 2020;10(10):1461. [Crossref] [pubMed] [pMC]
  • 5. Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, Shatford JL, et al. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum. 1997;40(10):1823- 8. [Crossref] [pubMed]
  • 6. van der Heijde D, Ramiro S, Landewé R, Baraliakos x, van den Bosch F, Sepriano A, et al. 2016 update of the ASAS-EuLAR management rec- ommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;76(6):978-91. [Crossref] [pubMed]
  • 7. Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA, et al. 2019 update of the American College of Rheumatology/Spondylitis As- sociation of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Non- radiographic Axial Spondyloarthritis. Arthritis Care Res (Hoboken). 2019;71(10):1285-99. [Crossref] [pubMed] [pMC]
  • 8. Moon KH, Kim YT. Medical treatment of ankylosing spondylitis. Hip pelvis. 2014;26(3):129-35. [Crossref] [pubMed] [pMC]
  • 9. Sayitoglu M. Kanser tedavisine farmakogenetik yaklaşım [Cancer ther- apy and pharmacogenetic approach: scientific letter]. Turkiye Klinikleri J Med Sci. 2007;27(3):434-41. [Link]
  • 10. Evans WE, Johnson JA. pharmacogenomics: the inherited basis for in- terindividual differences in drug response. Annu Rev Genomics Hum Genet. 2001;2:9-39. [Crossref] [pubMed]
  • 11. Sakaeda T. MDR1 genotype-related pharmacokinetics: fact or fiction? Drug Metab pharmacokinet. 2005;20(6):391-414. [Crossref] [pubMed]
  • 12. Jiang EZ, Chang YJ, Lee JW, Lee WK, Kim JS, Sohn SK, et al. Multi-drug resistance (MDR1) gene expression in de novo acute leukemia cells: correlations with CD surface markers and treatment outcome. J Korean Med Sci. 1998;13(6):617-22. [Crossref] [pubMed] [pMC]
  • 13. Baran Y, Gündüz u, ural Au. Expression of multi drug resistance (MDR1) gene in human promyelocytic leukemia cell line selected with vincristine. Turkish Journal of Cancer. 2005;35(2):88-92. [Link]
  • 14. Hoffmeyer S, Burk O, von Richter O, Arnold Hp, Brockmöller J, Johne A, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with p-glyco- protein expression and activity in vivo. proc Natl Acad Sci u S A. 2000;97(7):3473-8. [Crossref] [pubMed] [pMC]
  • 15. Jamroziak K, Balcerczak E, Cebula B, Janus A, Mirowski M, Robak T. No influence of 3435C>T ABCB1 (MDR1) gene polymorphism on risk of adult acute myeloid leukemia and p-glycoprotein expression in blast cells. Ther Drug Monit. 2006;28(5):707-11. [Crossref] [pubMed]
  • 16. Kimchi-Sarfaty C, Marple AH, Shinar S, Kimchi AM, Scavo D, Roma MI, et al. Ethnicity-related polymorphisms and haplotypes in the human ABCB1 gene. pharmacogenomics. 2007;8(1):29-39. [Crossref] [pubMed] [pMC]
  • 17. Schwab M, Eichelbaum M, Fromm MF. Genetic polymorphisms of the human MDR1 drug transporter. Annu Rev pharmacol Toxicol. 2003;43:285-307. [Crossref] [pubMed]
  • 18. Tanabe M, Ieiri I, Nagata N, Inoue K, Ito S, Kanamori Y, et al. Expression of p-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J pharmacol Exp Ther. 2001;297(3):1137-43. [pubMed]
  • 19. Akar S, Önen F. Ankilozan spondilit epidemiyolojisi [Epidemiology of ankylosing spondylitis]. Turkiye Klinikleri J Int Med Sci. 2007;3(27):1-12. [Link]
  • 20. Siddiqui A, Kerb R, Weale ME, Brinkmann u, Smith A, Goldstein DB, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med. 2003;348(15):1442- 8. [Crossref] [pubMed]
  • 21. Tang K, Ngoi SM, GweepC, Chua JM, Lee EJ, Chong SS, et al. Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 mul- tidrug transporter gene locus in three ethnic Asian populations. phar- macogenetics. 2002;12(6):437-50. [Crossref] [pubMed]
  • 22. Kim RB, Leake BF, Choo EF, Dresser GK, Kubba Sv, Schwarz uI, et al. Identification of functionally variant MDR1 alleles among European Amer- icans and African Americans. Clin pharmacol Ther. 2001;70(2):189-99. [Crossref] [pubMed]
  • 23. Gümüş-Akay G, Rüstemo ğlu A, Karadağ A, Sunguroğlu A. Haplotype- based analysis of MDR1/ABCB1 gene polymorphisms in a Turkish pop- ulation. DNA Cell Biol. 2010;29(2):83-90. [Crossref] [pubMed]
  • 24. Schaeffeler E, Eichelbaum M, Brinkmann u, penger A, Asante-poku S, Zanger uM, et al. Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet. 2001;358(9279):383-4. [Crossref] [pubMed]
  • 25. poller B, Drewe J, Krähenbühl S, Huwyler J, Gutmann H. Regulation of BCRp (ABCG2) and p-glycoprotein (ABCB1) by cytokines in a model of the human blood-brain barrier. Cell Mol Neurobiol. 2010;30(1):63-70. [Crossref] [pubMed]
APA Kurt Colak F, Bayram A, KORKMAZ BAYRAM K, KIRNAP M, Dundar M (2022). Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. , 213 - 220. 10.5336/medsci.2021-87249
Chicago Kurt Colak Fatma,Bayram Arslan,KORKMAZ BAYRAM KEZİBAN,KIRNAP MEHMET,Dundar Munis Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. (2022): 213 - 220. 10.5336/medsci.2021-87249
MLA Kurt Colak Fatma,Bayram Arslan,KORKMAZ BAYRAM KEZİBAN,KIRNAP MEHMET,Dundar Munis Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. , 2022, ss.213 - 220. 10.5336/medsci.2021-87249
AMA Kurt Colak F,Bayram A,KORKMAZ BAYRAM K,KIRNAP M,Dundar M Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. . 2022; 213 - 220. 10.5336/medsci.2021-87249
Vancouver Kurt Colak F,Bayram A,KORKMAZ BAYRAM K,KIRNAP M,Dundar M Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. . 2022; 213 - 220. 10.5336/medsci.2021-87249
IEEE Kurt Colak F,Bayram A,KORKMAZ BAYRAM K,KIRNAP M,Dundar M "Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research." , ss.213 - 220, 2022. 10.5336/medsci.2021-87249
ISNAD Kurt Colak, Fatma vd. "Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research". (2022), 213-220. https://doi.org/10.5336/medsci.2021-87249
APA Kurt Colak F, Bayram A, KORKMAZ BAYRAM K, KIRNAP M, Dundar M (2022). Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. Türkiye Klinikleri Tıp Bilimleri Dergisi, 42(3), 213 - 220. 10.5336/medsci.2021-87249
Chicago Kurt Colak Fatma,Bayram Arslan,KORKMAZ BAYRAM KEZİBAN,KIRNAP MEHMET,Dundar Munis Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. Türkiye Klinikleri Tıp Bilimleri Dergisi 42, no.3 (2022): 213 - 220. 10.5336/medsci.2021-87249
MLA Kurt Colak Fatma,Bayram Arslan,KORKMAZ BAYRAM KEZİBAN,KIRNAP MEHMET,Dundar Munis Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. Türkiye Klinikleri Tıp Bilimleri Dergisi, vol.42, no.3, 2022, ss.213 - 220. 10.5336/medsci.2021-87249
AMA Kurt Colak F,Bayram A,KORKMAZ BAYRAM K,KIRNAP M,Dundar M Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. Türkiye Klinikleri Tıp Bilimleri Dergisi. 2022; 42(3): 213 - 220. 10.5336/medsci.2021-87249
Vancouver Kurt Colak F,Bayram A,KORKMAZ BAYRAM K,KIRNAP M,Dundar M Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research. Türkiye Klinikleri Tıp Bilimleri Dergisi. 2022; 42(3): 213 - 220. 10.5336/medsci.2021-87249
IEEE Kurt Colak F,Bayram A,KORKMAZ BAYRAM K,KIRNAP M,Dundar M "Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research." Türkiye Klinikleri Tıp Bilimleri Dergisi, 42, ss.213 - 220, 2022. 10.5336/medsci.2021-87249
ISNAD Kurt Colak, Fatma vd. "Investigation of Relation Between MDR1 Gene and Ankylosing Spondylitis: Case Control Research". Türkiye Klinikleri Tıp Bilimleri Dergisi 42/3 (2022), 213-220. https://doi.org/10.5336/medsci.2021-87249