THE ROLE OF GLUTATION-S-TRANSFERASE MU1 AND TETA1 POLYMORPHISMS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Öz

Objective: The aim of this study the investigation of "null" alleles in GSTM1 and GSTT1 gene regions in the development of COPD disease.

Material and Method: There are 36 patients with COPD and 14 control cases, who received the Ethics Committee permission from Polatlı Duatepe State Hospital Chest Diseases Department. DNA isolations were made from blood samples from the end of 2019 and the control group. Deletions in GSTM1 and GSTT1 gene regions were examined by qPCR method in COPD patient and control groups. The results of the study were evaluated comparatively by distributing the gene dose according to the Hardy-Weinberg.

Result and Discussion: When seen from 36 COPD patients after qPCR analysis, it was found that deletion expressions due to gene doses in all patient groups; 23 individuals (63.8%) in the (+/-) genotype for GST-M1, 13 individuals (26.2%) in the (- / -) genotype. For GST-T1, 14 (%) in the (+ / +) genotype 38.8), while deletion was observed with the highest rate, 4 individuals (11.1%) in the (+/-) genotype and 18 individuals (50.1%) in the (- / -) genotype were found. For GST-M1, deletion was observed in 19 individuals (63.3%) in the genotype (+/-) in male individuals, while it was observed in 4 individuals (66.6%) with the same genotype in women. While deletion was not observed in 11 (36.6%) male patients, this rate was observed as 2 (33.4%) in women. In the GST-T1 gene region, there were 10 (33.3%) males in male patients and 4 (66.6%) individuals in female patients with deletion occurring and the frequency of the "null allele" was high (+ / +). In the (+/-) genotype, 3 (10%) in males and 1 (16.7%) in females were found. In the genotype where deletion was not observed and the gene was conserved (- / -), 17 (56.7%) individuals were observed in male patients and 1 (16.7%) in female patients. In the case that the gene "null" allele status in the GST-M1 gene region is slightly higher than the GST-T1 gene communication, this situation is thought to be a factor in obstructive pulmonary disease.

Anahtar Kelimeler

• Deletion
• GST Isozymes
• COPD
• qPCR

KRONİK OBSTRÜKTİF AKCİĞER HASTALIĞINDA GLUTATYON-S-TRANSFERAZ MU1 VE TETA1 POLİMORFİZMLERİNİN ROLÜ

Öz

Amaç: Çalışmamızın amacı, KOAH hastalığının oluşumunda GSTM1 ve GSTT1 gen bölgesindeki “null” allellerinin rolü olup olmadığını araştırmaktır.

Gereç ve Yöntem: Bu çalışmada, Polatlı Duatepe Devlet Hastanesi Göğüs hastalıkları bölümünden Etik Kurul izni alınmış 36 KOAH’lı hasta ve 14 kontrol vakası bulunmaktadır. 2019 yılı içerisinde hasta ve kontrol grubundan alınmış olan kan örneklerinden DNA izolasyonları yapıldı. KOAH hasta ve kontrol grubunda qPCR metodu ile GSTM1 ve GSTT1 gen bölgelerinde ki delesyon durumları incelendi. Çalışmanın sonuçları Hardy-Weinberg, Chi-Squared ve fisher’s exact kuralına göre gen dozu seviyesinde dağılımları yapılarak karşılaştırmalı olarak değerlendirmeye alındı.

Sonuç ve Tartışma: Yapılan qPCR analizleri sonrası 36 KOAH hastasından alınan numunelerde, tüm hasta grubunda gen dozlarına bağlı delesyon ifadelerinden; GST-M1 için (+/-) genotipinde 23 birey (%63,8), (-/-) genotipinde 13 birey (%26,2) şeklinde gözlemlenmiştir. GST-T1 için, (+/+) genotipinde 14 bireyde (%38,8) delesyon en yüksek oranda gözlemlenirken, (+/-) genotipinde 4 bireye (%11,1) ve (-/-) genotipinde 18 bireye (%50,1) rastlanmıştır. GST-M1 için erkek bireylerde (+/-) genotipinde delesyon 19 bireyde (%63,3) gözlemlenirken kadınlarda aynı genotipte 4 bireyde (%66,6) şeklinde gözlemlenmiştir. Erkeklerde 11(%36,7) hastada GST-M1 delesyonu gözlemlenmezken, bu oran kadınlarda 2(%33,4) şeklinde gözlemlenmiştir. GST-T1 de bu durum delesyonun gerçekleştiği ve “null allel” frekansının yüksek olarak gözlemlendiği (+/+) genotipinde erkek hastalarda 10(%33,3), kadın hastalarda ise 4(%66,6) bireye rastlanmıştır. (+/-) Genotipinde erkeklerde 3(%10) kadınlarda ise 1(%16,7) bireye rastlanmıştır. Delesyonun gözlemlenmediği ve genin korunduğu (-/-) genotipinde erkek hastalarda 17(%56,7), kadın hastalarda ise 1(%16,7) birey gözlemlenmiştir. Yapmış olduğumuz çalışmada, GST-M1 gen bölgesinde gen “null” allel durumunun GST-T1 gen bölgesine göre bir miktar daha fazla olduğu belirlenmiş olup bu durumun kronik obstrüktif akciğer hastalığında etken olduğu düşünülmektedir.

Anahtar Kelimeler

• Delesyon
• GST İzozimleri
• KOAH
• qPCR

Kaynakça

1. 1. Celi BR, MacNee W. Standarts fort he diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004; 23: 932.
2. 2. Menezes AM, Perez-Padilla P, Jardim JR, et al. Chronic obstructive pulmonary disease in five Latin American cities (the PLATİNO study): a prevalence study. Lancet 2005; 366: 1875-81.
3. 3. Gunen H, Hacievliyagil SS, Yetkin O, et al. Prevalence of COPD: first epidemiological study of a large region in Turkey. Eur J Intern Med 2008; 19: 499-504.
4. 4. Oulette DR. The answer is fifteen percent: what is the question? Chest 2004;125:3-5.
5. 5. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095-128.
6. 6. http://www.who.int/respiratory/copd/burden/en/index.html (Erişim tarihi; 24.03.2010).
7. 7. Global Initiative for Chronic Obstructive Lung Disease: Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (Güncelleme 2016).
8. 8. McGinnis JM, Williams-Russo P, Knickman JR. The case for more active policy attention to health promotion. Health Affairs 2012;21:78-93.

9. 9. Hooper R, Burney P, Vollmer WM, et al. Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD Project. Eur Respir J 2012;39:1343-53.
10. 10. Crawford EL, Khuder SA, Durham SJ, Frampton M, Utell M, Thilly WG, et al. Normal bronchial epithelial cell expression of glutathione transferase P1, glutathione transferase M3, and glutathione peroxidase is low in subjects with bronchogenic carcinoma. Cancer Res 2000: 60: 1609-18.
11. 11. Han W, Pentecost BT, Pietropaolo RL, Fasco MJ, Spivack SD. Estrogen receptor alpha increases basal and cigarette smoke extract-induced expression of CYP1A1 and CYP1B1, but not GSTP1, in normal human bronchial epithelial cells. Mol Carcinog 2005; 44: 202-11.
12. 12. Landi S. Mammalian class theta GST and differential susceptibility to carcinogens: a review. Mutat Res 2000; 463: 247-83.
13. 13. Teramoto S. 1. COPD Pathogenesis from the Viewpoint of Risk Factors. Japanese Journal of Medicine 2007: 46: 77-79.
14. 14. Ding Z, Wang K, Li J, Tan Q, Tan W, Guo G. Association between glutathione S-transferase gene M1 and T1 polymorphisms and chronic obstructive pulmonary disease risk: a meta-analysis. Clin Genet 2019;95:53–62.
15. 15. Hemimi NED, Attar MA, Abd Elwahab MA. Genetic Polymorphism Of Glutathione-S Transferase And Susceptibility To And Severity Of Chronic Obstructive Pulmonary Disease. The FASEB Journal. 2009: 27: 117-128.
16. 16. Vasudevan, Sreekumarı, & Vaıdyanathan, 2011)-( Vasudevan, D., Sreekumarı, S., & Vadyanathan, K. (2011). Textbook Of Biochemistry For Medical Students (Sixth Edition b.). New Delhi India: Jaypee Brothers Medical Publishers (P) Ltd,).
17. 17. Girault I, Lidereau R, Bièche I. Trimodal GSTT1 and GSTM1 genotyping assay by real-time PCR. Int J Biol Markers. 2005 Apr-Jun;20(2):81-6. PMID: 16011037.
18. 18. Vogelmeier CF, Criner GJ, Martinez FJ et al. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Respirology 2017: 22: 575-601.
19. 19. Strange RC, Fryer AA. The glutathione S-transferases: influence of polymorphism on cancer susceptibility. Iarc Scientific Publications 1999: 148: 231.
20. 20. Hu G, Yao W, Zhou Y et al. Meta- and pooled analyses of the effect of glutathione S transferase M1 and T1 deficiency on chronic obstructive pulmonary disease. International Journal of Tuberculosis & Lung Disease the Official Journal of the International Union Against Tuberculosis & Lung Disease 2008: 12: 1474 1481.
21. 21. Shukla RK, Kant S, Bhattacharya S et al. Association of Genetic Polymorphism of GSTT1, GSTM1 and GSTM3 in COPD Patients in a North Indian Population. Copd Journal of Chronic Obstructive Pulmonary Disease 2011: 8: 167-172.
22. 22. Tkacova R, Salagovic J, Ceripkova M et al. Glutathione S-transferase M1 gene polymorphism is related to COPD in patients with non-small-cell lung cancer. Wiener Klinische Wochenschrift 2004: 116: 131-134.
23. 23. Castaldi PJ, Cohn CM, Langerman F et al. The COPD genetic association compendium: a comprehensive online database of COPD genetic associations. Human Molecular Genetics 2010: 19: 526.
24. 24. Dimov D, Vlaykova T, Kurzawski M et al. Effect of genetic polymorphisms of some cytokines and xenobiotic-metabolizing enzymes on the lung function in patients with COPD. European Respiratory Journal 2012: 1750.
25. 25. Silverman EK, Weiss ST, Drazen JM, et al. Gender relateddifferences in severe, early onset chronic obstructivepulmonary disease. Am J Respir Crit Care Med 2000; 162:2152–2158.
26. 26. Pilar C-G, Javier M-D, Javier R-G, Antonio M-Co, Elena G-V, Valentin H B, Angel G M, Rodrigo J-G, Characteristics of chronic obstructive pulmonary disease in Spain from a gender perspective BMC Pulmonary Medicine prepublished online 2009; 9:2.