Comparative analysis of GSTM1/GSTT1 null alleles and Ile105Val GSTP1 variant in patients with Nasal Polyposis and hyposmia in a Romanian population group

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Abstract

Background. Polymorphisms for genes encoding glutathione S-transferase (GSTM1/GSTT1/GSTP1) might be one of the factors that can influence the variability in susceptibility for hyposmia in normal and ENT pathology associated individuals. The role of GST family enzyme might be important in exposure to xenobiotic induced damage of nasal mucosa. Objectives. To evaluate of distribution of GST variants (GSTM1/GSTT1 null alleles and Ile105Val GSTP1 polymorphism) among patients with hyposmia and normal individuals by using a case-control study. Subjects The study included 75 cases of hyposmic patients (evaluated with “Sniffin’ Sticks” olfaction Test), recruited from the Otorhinolaryngology Department of Emergency County Hospital, Cluj-Napoca and 124 healthy unrelated controls. Methods. GSTM1 and GSTT1 variants genotyping was accomplished using a Multiplex PCR method, followed by agarose gel electrophoresis. GSTP1 Ile105Val gene variant was genotyped using PCR-RLFP technique. Results. Comparative analysis for Ile105Val variant of GSTP1 gene revealed no statistical differences among patients and controls (χ2 = 3.012, p = 0.087, OR = 1.514, CI = 0.491 to 1.572). Molecular analysis did not reveal an increased frequency for GSTT1 and GSTM1 null alleles in the patients group compared to controls (GSTT1 - 95% CI = 0.332 to 1.261, p = 0.192, OR = 0.641, χ2 = 2.120, GSTM1 - 95% CI = 0.171 to 0.592, χ2 = 2.017, OR = 0.321, p = 0.062). Significant statistical differences were found when combined GSTM1 and GSTT1 null genotypes (double-null genotypes) were compared between patients and controls (p=0.0015, OR=4.0351; CI=1.706-9.543) and when comparing allergic NP patients with non-allergic NP patients (p=0.027, OR=3.455, CI=1.147-10.406). Conclusions. The presence of both GSTM1/GSTT1 null genotypes (double null genotypes) is considered to be a risk factor for NP and hyposmia development in allergic individuals. The results of our study show no correlation between Ile105Val polymorphism of GSTP1 gene and nasal polyposis associated hyposmia in this Romanian group population.

1. Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000. 61(3):154-66.

2. Nebert DV, Vasiliou V. Analysis of the glutathione Stransferase (GST) gene family. Human Genomics 2004;1:460-464.

3. Hayes JD, Pulford DJ. The Glutathione S Transferase supergene family regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. rev Biochem Mol. Biol 1995;30:445-600.

4. Ketterer B, Christodoulides LG. Enzymology of cytosolic glutathione S-transferases. Adv.Pharmacol 1994;27:37-69.

5. Tamer L , Calıkoglu M, AteS NA, Yıldırım H , Ercan B , Sarıtas E et al. Glutathione-S-Transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma. Respirology 2004;9:493-498.

6. Tamer L , Ercan B, Camsarı A, Yıldırım H, Cicek D, Sucu N et al. Glutathione-S-transferase gene polymorphism as a susceptibility factor in smoking related coronary artery disease. Basic Res Cardiol 2004;99:223-229.

7. McIlwain CC, Townsend DM, Tew KD. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene 2006;25(11):1639-48.

8. Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA. Human glutathione-S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 1998;19:275-280.

9. Seidegard J, Vorachek WR, Pero RW. Hereditary differences in the expression of the human Glutathione transferase active on trans-stilbene oxide are due to a gene deletion. Proc Natl Acad Sci USA 1988;85:7293-7297.

10. Rebbeck TR. Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol. Biomarkers Prev. 1997 Sep;6(9):733-43.

11. Arbaq H, Cora T, Acar H, Ozturk K, Sari F, Ulusoy B. Lack of association between the glutathione-S-transferase genes (GSTT1 and GSTM1) and nasal polyposis. Rhinology 2006; 44:14-18.

12. Dali AK. Molecular basis of polymorphic drug metabolism. J Mol.Med, 1995, 73:539-553.

13. Zuntar I, Kalanj-Bognar S, Popic E, Petlevki R, Stefanocic M, Demarin V. The glutathione S-transferase polymorphisms in a control population and in Alzheimer's disease patients. Clin Chem Lab Med 2004;42(3):334-9.

14. Ben-Arie N, Khen M, Lancet D. Glutathione S-transferases in rat olfactory epithelium: purification, molecular properties and odorant biotransformation. Biochem J. 1993 Jun 1;292(Pt 2):379-84.

15. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. ‘Sniffin’sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses. 1997;22:39-52.

16. Kobal G, Klimek L, Wolfensberger M, Gudziol H, Temmel A, Owen CM, Seeber H, Pauli E, Hummel T. Multicenter investigation of 1036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur Arch Otorhinolaryngol. 2000;257: 205-211.

17. Catana I, Negoias S, Maniu A, Porojan M, Cosgarea M. A modified version of “Sniffin’Sticks” odor identification test: The Romanian cultural adaptation. Clujul Medical 2012;85;2:218-223.

18. Dogru H, Delibas N, Doner F, Tuz M. Free radical damage in nasal polyp tissue. Otolaryngol Head Neck Surg 2001;124:570-572.

19. Fokkens W, Lund V, Mullol J. European position paper on rhinosinusitis and nasal polyps. Rhinol Suppl. 2007:1-136.

20. Dagli M, Erylmaz A, Besler T, Akmansu H, Acar A, Korkmaz H. Role of free radicals and antioxidants in nasal polyps. Laryngoscope 2004;114:1200-1203.

21. Ruwali M, Singh M, Pant MC, Parmar D. Polymorphism in glutathione S-transferases: susceptibility and treatment outcome for head and neck cancer. Xenobiotica. 2011;1122-1130.

22. Jourenkova-Mironova N, Voho A, Bouchardy C, Wikman H, Dayer P, Benhamou S, et al. Glutathione Stransferase GSTM3 and GSTP1 genotypes and larynx cancer risk. Cancer Epidemiol. Biomarkers Prev. 1999 Feb;8(2):185-8.

23. Ozcan C, Tamer L, Ates NA, Görür K. The glutathione- S-transferase gene polymorphisms (Gstt1, Gstm1, and Gstp1) in patients with non-allergic nasal polyposis. Eur Arch Otorhinolaryngol. 2010;267:227-32.

24. Hanene C, Jihene L, Jamel A, Kamel H, Agnes H. Association of GST genes polymorphisms with asthma in Tunusian children. Mediators Inflamm. 2007;10;1155.19564, DOI: 10.1155/2007/19564

25. Brutsche M, Schindler C, Downs SH, Gerbase MW, Berger W, Probst-Hensch NM SAPALDIA Team Glutathione- Stransferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults. Thorax 2008;63:322-328.

26. Imboden M, Rochat T, Holla LI, Stejskalova A, Vasku A. Polymorphism of the GSTM1 and GST1 genes in patients with allergic diseases in the Czech population. Allergy 2006;61:265-267.

27. Carrol WD, Lenney PW, Jones PW, Strange RC, Child F, Whyte MK, Primhak RA, Fryer AA, Effects of glutathione-stransferase M1, T1 and P1 on lung function in asthmatic families. Clin Exp Allergy 2005;35:1155-1161.

28. Figueiredo CR, Santos RP, Silva ID, Weckx LL. Microarray cDNA to identify inflammatory genes in nasal polyposis. American journal of rhinology. 2007 Mar- Apr;21(2):231-5.

29. Erbek SS, Yurtcu E, Erbek S, Atac FB, Sahin FI, Cakmak O. Proinflammatory cytokine single nucleotide polymorphisms in nasal polyposis. Archives of otolaryngology-- head & neck surgery. 2007 Jul;133(7):705- 9.

30. Anand VK, Kacker A, Orjuela AF, Huang C, Manarey C, Xiang J. Inflammatory pathway gene expression in chronic rhinosinusitis. American Journal of rhinology. 2006 Jul-Aug;20(4):471-6.

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

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