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Diyabetik Nefropatili Hastalarda Paraoksonaz 1 Gen Polimorfizmlerinin Araştırılması

Year 2022, Volume: 19 Issue: 2, 230 - 238, 28.08.2022
https://doi.org/10.35440/hutfd.1142132

Abstract

Amaç:. Bu çalışmada, Paraoksonaz 1 geni kodlanan bölge Q192R ve L55M polimorfizmleri ile Tip2 Diyabetli hastalarda Diyabetik Nefropati gelişimi arasındaki ilişkinin araştırılması amaçlandı. Materyal ve metod: Harran Üniversitesi Tıp Fakültesi Endokrinoloji Bilim Dalı polikliniklerine başvuran; Tip2 Diyabetli 50 hasta ( 25 erkek, 25 kadın; ort. yaş 52.06±8.43), Diyabetik Nefropatili 50 hasta ( 24 erkek, 26 kadın; ort. yaş 50.94±10.75) ve 50 sağlıklı kontrol (12 erkek, 38 kadın; ort. yaş 50.42±11.062) grupları çalışmaya alındı. Alınan periferik kan örneklerinden DNA izolasyonu yapıldı. Polimeraz zincir reaksiyonu ile elde edilen ürünler restriksiyon enzimleri AlwI ve Hin1II ile kesildi. Elde edilen ürünler agaroz jelde yürütüldü. UV görüntüleme ile polimorfizm genotiplemesi yapıldı. Bulgular: Paraoksonaz 1 geni Q192R (584A/G) polimorfizmini genotip dağılımı: Tip 2 Diyabet hasta grubunda; QQ %58, QR %32 ve RR %10 bulundu. Diyabetik Nefropati grubunda; QQ %52, QR %42 ve RR %6 bulundu. Sağlıklı kontrol grubunda; QQ %62 , QR %30 ve RR %8 bulundu. Gruplar arasında genotip frekansları yönünden istatistiksel olarak anlamlı bir fark görülmedi (p>0.05). Paraoksonaz 1 geni L55M (172T/A) polimorfizminin genotip dağılımı: Tip 2 Diyabet hasta grubunda LL %48, LM %32 ve MM %20 bulundu. Diyabetik Nefropati grubunda; LL %68, LM %26 ve MM %6 bulundu. Sağlıklı kontrol grubunda; LL %42, LM %42 ve MM %16 bulundu. Gruplar arasında genotip dağılımı yönünden istatistiksel olarak anlamlı bir fark görülmedi (p>0.05). M allel frekansının Tip 2 DM’li ve DN’li grupta istatistiksel olarak anlamlı olduğu görüldü (sırasıyla p=0.007, p=0.011).
Sonuç: Bulgularımıza göre, Paraoksonaz 1 L55M allel frekansının, Tip2 Diyabet ve Diyabetik Nefropati hasta grubunda anlamlı çıkması, Paraoksonaz 1 L55M polimorfizminin bu hastalıkların gelişiminde risk faktörü olabileceğini düşündürmektedir. Paraoksonaz 1 geni Q192R ve L55M polimorfizmlerinin, Tip 2 Diyabet hastalarında Diyabetik Nefropatiye yakalanma riski ile ilişkili olmadığı görüldü.

Supporting Institution

Harran Üniversitesi Bilimsel Araştırma Projeleri

Project Number

19251

Thanks

Yüksek Lisans Öğrencisi Uzman Oğuzhan KENGER, çalışmaya katkısı olmuş ancak makalenin yazım aşamasında vefat etmiştir. Kendisine yapmış olduğu katkılardan dolayı teşekkür ederiz.

References

  • 1. Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, et al. Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus, Diabetes Research and Clinical Practice, 2002;55, 65-85.
  • 2. Amaral S, Oliveira P J, Ramallo-Santos J. Diabetes and the Impairment of Reproductive Function: Possible Role of Mitochondria and Reactive Oxygen Species, Current Diabetes Reviews, 2008;4, 46-54.
  • 3. Puavilai G, Chanprasertyotin S, Sriphrapradaeng A. Diagnostic Criteria for Diabetes Mellitus and Other Categories of Glucose Intolerance: 1997 Criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO Consultation Criteria, and 1985 WHO Criteria, Diabetes Research and Clinical Practice, 1999;44, 21-26.
  • 4. Heydari I, Radi V, Razmjou S, Amiri A. Chronic Complications of Diabetes Mellitus in Newly Diagnosed Patients, International Journal of Diabetes Mellitus, 2010;2(1), 61-63.
  • 5. Ryden L, Standhl E, Bartnik M, Berghe GVD, Betteridge J. Guidelines on diabetes, pre-diabetes, and cardiovascular disease. EurHeart J 2007; 28: 88-136.
  • 6. D Deshpande A, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008;88(11):1254-64.
  • 7. Cho NH, Kirigia J, Mbanya JC, Ogurstova K, Guariguata L, Rathmann W et al. Diabetes Atlas. International Diabetes Federation. 8th edition, 2017; 14(5):120-40.
  • 8. Said G. Diabetic Neuropathy: An update. J Neurol 1996; 243(6):431-40.
  • 9. Lippert J, Ritz E, Schawarzberg A, Schneider P. The rising tide of end-stage renal failure from diabetic nephropathy type II—an epidemiological analysis. Nephrol Dial Transplant 1995; 10: 462-7.
  • 10. Bingöl G., Topbaş E. Diyabetik Nefropati Evreleri ve Evrelere Özgü Hemşirelik Yaklaşımı. Türk Nefroloji, Diyaliz ve Transplantasyon Hemşireleri Derneği Nefroloji Hemşireliği Dergisi 2018:2 (13).
  • 11. Motti C, Dessì M, Gnasso A, Irace C, Indigeno P, Angelucci CB, et al. A multiplex PCR-based DNA assay for the detection of paraoxonase gene cluster polymorphisms. Atherosclerosis 2001;158:35-40.
  • 12. Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest. 1998; 101(8):1581-1590.
  • 13. Mackness MI, Durrington PN. HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis. 1995; 115(2): 243-253.
  • 14. Costa LG., Vitalone A., Cole TB., Furlong. Modulation of Paraoxonase (PON1) activity Biochem Pharmacol. 2005; 69 : 541-550.
  • 15. Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1 Clinical Science 2004;107: 435-447.
  • 16. Aviram M. Does paraoxonase play a role in susceptibility to cardiovascular disease? Mol Med Today 1999;5:381-6.
  • 17. Özdemir İ., Hocaoğlu Ç. Tip 2 diabetes mellitus ve yaşam kalitesi: Bir gözden geçirme. Göztepe Tıp Dergisi 2009;24(2):73-78.
  • 18. Kahn B B. Type 2 Diabetes: When Insulin Secretion Fails to Compensate for Insulin Resistance, Cell, 1998;92, 593-596.
  • 19. Satman İ. ve TURDEP Çalışma Grubu. (2011)
  • 20. Groop LC, Widen E, Ferrannini E. Insulin resistance and insulin deficiency in pathogenesis of type 2 diabetes. Errors of metabolism or methods. Diabetologia 36: 1326-1331, 1993.
  • 21. Tsai FJ, Yang CF, Chen CC, Chuang LM, Lu CH, Chang CT, et al,. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet, 2010; 19;6(2).
  • 22. 91. Rizvi S., Raza S.T., Mahdi F. Association of genetic variants with diabetic nephropathy, World J Diabetes. 2014 Dec 15;5(6):809-16. doi: 10.4239/wjd.v5.i6.809.
  • 23. Adkins S, Gan KN, Mody M,La Du BN. Molecular basis fort he polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, fort he respective A or Ballozymes. Am J Hum Genet 1993;52:598-608.
  • 24. Fortunato G, Rubba P, Panico S, Trono D, Tinto N, Mazzaccara C, et al. A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women. Atherosclerosis 2003;167(1):141-8.
  • 25. Voetsch B, Benke KS, Damasceno BP, Siqueira LH, Loscalzo J. Paraoxonase 192 Gln-->Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults. Stroke 2002;33(6):1459- 64.
  • 26. Sanghera DK, Saha N, Aston CE, Kamboh MI. Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol 1997;17(6):1067-73.
  • 27. Antikainen M, Murtomäki S, Syvänne M, Pahlman R, Tahvanainen E, Jauhiainen M, et al. The Gln-Arg191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Finns. J Clin Invest 1996;98(4):883-5.
  • 28. Liu H, Xia P, Liu M, Ji XM, Sun HB, Tao L, et al. PON gene polymorphisms and ischaemic stroke: a systematic review and meta analysis. Int J Stroke. 2013;8(2):111-123.
  • 29. Araki S, Makita Y, Canani L, Ng D, Warram J.H, Krolewski A.S. Polymorphisms of human paraoxonase 1 gene (PON1) and susceptibility to diabetic nephropathy in Type I diabetes mellitus, Diabetologia 2000;43,1540–1543.
  • 30. Fekih O, Triki S, Rejeb J, Neffati F, Douki W, Ommezzine A, et al., Paraoxonase 1 polymorphisms (L55M and Q192R) as a genetic marker of diabetic nephropathy in youth with type 1 diabetes, Endokrynologia Polska 2017;68(1):35-41.
  • 31. Wang J, Yang MM, Rong SS, Ng TK, Li YB, Liu XM. Association of paraoxonase gene polymorphisms with diabetic nephropathy and retinopathy, Molecular Medicine Reports, 2013, 1845-1851.
  • 32. Grzegorzewska AE, Ostromecka K, Adamska P, Mostowska A, Warchoł W, Jagodziński PP. Paraoxonase 1 gene polymorphisms concerning non-insulin-dependent diabetes mellitus nephropathy in hemodialysis patients, Journal of Diabetes and its Complications, 2020;34,(11), 107687.
  • 33. Li C, Gu Ç. Protective effect of paraoxonase 1 of high-density lipoprotein in type 2 diabetic patients with nephropathy, Nephrology (Carlton), 2009;14(5):514-20.
  • 34. Qujeq D, Mahrooz A, Alizadeh A, Masoumi P, Annemohammadzadeh S, Boorank R. Genotype and phenotype of salt-stimulated paraoxonase 1 (PON1) is associated with atherogenic indices in type 2 diabetes, J Diabetes Metab Disord. 2018;17(1): 1–10.
  • 35. Ayan D, Şeneş M, Çaycı AB, Söylemez S, Eren N, Altuntaş Y, et al,. Evaluation of Paraoxonase, Arylesterase, and Homocysteine Thiolactonase Activities in Patients with Diabetes and Incipient Diabetes Nephropathy, J Med Biochem. 2019;38(4): 481–488.

Investigation of Paraoxonase 1 Gene Polymophisms In Patients With Diabetic Nephropathy

Year 2022, Volume: 19 Issue: 2, 230 - 238, 28.08.2022
https://doi.org/10.35440/hutfd.1142132

Abstract

Background: In this study, it was aimed to investigate the relationship between Q192R and L55M polymorphisms in the region encoding the Paraoxonase 1 (PON1) gene and the development of Diabetic Nephropathy in patients with Type 2 Diabetes.
Materials and Methods: Applying to Harran University Medical Faculty Endocrinology Department polyclinics; 50 patients with Type 2 Diabetes, 50 patients with Diabetic Nephropathy and 50 healthy controls groups were included in the study. DNA isolation was performed from peripheral blood samples. The products obtained by polymerase chain reaction were cut with the restriction enzymes AlwI and Hin1II. The obtained products were run on an agarose gel. Polymorphism genotyping was performed by UV imaging.
he study was planned as descriptive cross-sectional. The attitudes of the students studying at the Faculty of medicine towards scientific research were questioned. In the study, the ‘’Attitude Scale Towards Scientific Research ‘’ was used.
Results: The genotype distribution of the paraoxonase 1 gene Q192R (584A/G) polymorphism: It was found QQ 58%, QR 32%, and RR 10% in Type 2 Diabetes patient group. It was found QQ 52%, QR 42%, and RR 6% in Diabetic Neph-ropathy group. It was found QQ 62%, QR 30%, and RR 8% in healthy control group. There was no statistically signifi-cant difference between the groups in terms of genotype frequencies (p>0.05). Genotype distribution of Paraoxona-se 1 gene L55M (172T/A) polymorphism:It was found LL 48%, LM 32%, and MM 20% in Type 2 Diabetes patient group. It was found LL 68%, LM 26%, and MM 6% in Diabetic Nephropathy group. It was found LL 42%, LM 42%, and MM 16% in healthy control group. There was no statistically significant difference between the groups in terms of genotype frequencies (p>0.05). M allele frequency was found to be statistically significant in Type 2 Diabetes and Diabetic Nephropathy groups (p=0.007, p=0.011, respectively).
Conclusions: According to our findings, the fact that Paraoxonase 1 L55M allele frequency was significant in Type 2 Diabetes and Diabetic Nephropathy patient groups suggests that Paraoxonase 1 L55M polymorphism may be a risk factor in the development of these diseases. Paraoxonase 1 gene Q192R and L55M polymorphisms were not associa-ted with the risk of developing Diabetic Nephropathy in Type 2 Diabetes patients.

Project Number

19251

References

  • 1. Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, et al. Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus, Diabetes Research and Clinical Practice, 2002;55, 65-85.
  • 2. Amaral S, Oliveira P J, Ramallo-Santos J. Diabetes and the Impairment of Reproductive Function: Possible Role of Mitochondria and Reactive Oxygen Species, Current Diabetes Reviews, 2008;4, 46-54.
  • 3. Puavilai G, Chanprasertyotin S, Sriphrapradaeng A. Diagnostic Criteria for Diabetes Mellitus and Other Categories of Glucose Intolerance: 1997 Criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO Consultation Criteria, and 1985 WHO Criteria, Diabetes Research and Clinical Practice, 1999;44, 21-26.
  • 4. Heydari I, Radi V, Razmjou S, Amiri A. Chronic Complications of Diabetes Mellitus in Newly Diagnosed Patients, International Journal of Diabetes Mellitus, 2010;2(1), 61-63.
  • 5. Ryden L, Standhl E, Bartnik M, Berghe GVD, Betteridge J. Guidelines on diabetes, pre-diabetes, and cardiovascular disease. EurHeart J 2007; 28: 88-136.
  • 6. D Deshpande A, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008;88(11):1254-64.
  • 7. Cho NH, Kirigia J, Mbanya JC, Ogurstova K, Guariguata L, Rathmann W et al. Diabetes Atlas. International Diabetes Federation. 8th edition, 2017; 14(5):120-40.
  • 8. Said G. Diabetic Neuropathy: An update. J Neurol 1996; 243(6):431-40.
  • 9. Lippert J, Ritz E, Schawarzberg A, Schneider P. The rising tide of end-stage renal failure from diabetic nephropathy type II—an epidemiological analysis. Nephrol Dial Transplant 1995; 10: 462-7.
  • 10. Bingöl G., Topbaş E. Diyabetik Nefropati Evreleri ve Evrelere Özgü Hemşirelik Yaklaşımı. Türk Nefroloji, Diyaliz ve Transplantasyon Hemşireleri Derneği Nefroloji Hemşireliği Dergisi 2018:2 (13).
  • 11. Motti C, Dessì M, Gnasso A, Irace C, Indigeno P, Angelucci CB, et al. A multiplex PCR-based DNA assay for the detection of paraoxonase gene cluster polymorphisms. Atherosclerosis 2001;158:35-40.
  • 12. Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest. 1998; 101(8):1581-1590.
  • 13. Mackness MI, Durrington PN. HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis. 1995; 115(2): 243-253.
  • 14. Costa LG., Vitalone A., Cole TB., Furlong. Modulation of Paraoxonase (PON1) activity Biochem Pharmacol. 2005; 69 : 541-550.
  • 15. Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1 Clinical Science 2004;107: 435-447.
  • 16. Aviram M. Does paraoxonase play a role in susceptibility to cardiovascular disease? Mol Med Today 1999;5:381-6.
  • 17. Özdemir İ., Hocaoğlu Ç. Tip 2 diabetes mellitus ve yaşam kalitesi: Bir gözden geçirme. Göztepe Tıp Dergisi 2009;24(2):73-78.
  • 18. Kahn B B. Type 2 Diabetes: When Insulin Secretion Fails to Compensate for Insulin Resistance, Cell, 1998;92, 593-596.
  • 19. Satman İ. ve TURDEP Çalışma Grubu. (2011)
  • 20. Groop LC, Widen E, Ferrannini E. Insulin resistance and insulin deficiency in pathogenesis of type 2 diabetes. Errors of metabolism or methods. Diabetologia 36: 1326-1331, 1993.
  • 21. Tsai FJ, Yang CF, Chen CC, Chuang LM, Lu CH, Chang CT, et al,. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet, 2010; 19;6(2).
  • 22. 91. Rizvi S., Raza S.T., Mahdi F. Association of genetic variants with diabetic nephropathy, World J Diabetes. 2014 Dec 15;5(6):809-16. doi: 10.4239/wjd.v5.i6.809.
  • 23. Adkins S, Gan KN, Mody M,La Du BN. Molecular basis fort he polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, fort he respective A or Ballozymes. Am J Hum Genet 1993;52:598-608.
  • 24. Fortunato G, Rubba P, Panico S, Trono D, Tinto N, Mazzaccara C, et al. A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women. Atherosclerosis 2003;167(1):141-8.
  • 25. Voetsch B, Benke KS, Damasceno BP, Siqueira LH, Loscalzo J. Paraoxonase 192 Gln-->Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults. Stroke 2002;33(6):1459- 64.
  • 26. Sanghera DK, Saha N, Aston CE, Kamboh MI. Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol 1997;17(6):1067-73.
  • 27. Antikainen M, Murtomäki S, Syvänne M, Pahlman R, Tahvanainen E, Jauhiainen M, et al. The Gln-Arg191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Finns. J Clin Invest 1996;98(4):883-5.
  • 28. Liu H, Xia P, Liu M, Ji XM, Sun HB, Tao L, et al. PON gene polymorphisms and ischaemic stroke: a systematic review and meta analysis. Int J Stroke. 2013;8(2):111-123.
  • 29. Araki S, Makita Y, Canani L, Ng D, Warram J.H, Krolewski A.S. Polymorphisms of human paraoxonase 1 gene (PON1) and susceptibility to diabetic nephropathy in Type I diabetes mellitus, Diabetologia 2000;43,1540–1543.
  • 30. Fekih O, Triki S, Rejeb J, Neffati F, Douki W, Ommezzine A, et al., Paraoxonase 1 polymorphisms (L55M and Q192R) as a genetic marker of diabetic nephropathy in youth with type 1 diabetes, Endokrynologia Polska 2017;68(1):35-41.
  • 31. Wang J, Yang MM, Rong SS, Ng TK, Li YB, Liu XM. Association of paraoxonase gene polymorphisms with diabetic nephropathy and retinopathy, Molecular Medicine Reports, 2013, 1845-1851.
  • 32. Grzegorzewska AE, Ostromecka K, Adamska P, Mostowska A, Warchoł W, Jagodziński PP. Paraoxonase 1 gene polymorphisms concerning non-insulin-dependent diabetes mellitus nephropathy in hemodialysis patients, Journal of Diabetes and its Complications, 2020;34,(11), 107687.
  • 33. Li C, Gu Ç. Protective effect of paraoxonase 1 of high-density lipoprotein in type 2 diabetic patients with nephropathy, Nephrology (Carlton), 2009;14(5):514-20.
  • 34. Qujeq D, Mahrooz A, Alizadeh A, Masoumi P, Annemohammadzadeh S, Boorank R. Genotype and phenotype of salt-stimulated paraoxonase 1 (PON1) is associated with atherogenic indices in type 2 diabetes, J Diabetes Metab Disord. 2018;17(1): 1–10.
  • 35. Ayan D, Şeneş M, Çaycı AB, Söylemez S, Eren N, Altuntaş Y, et al,. Evaluation of Paraoxonase, Arylesterase, and Homocysteine Thiolactonase Activities in Patients with Diabetes and Incipient Diabetes Nephropathy, J Med Biochem. 2019;38(4): 481–488.
There are 35 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Feridun Akkafa 0000-0002-9292-2410

Oğuzhan Kenger This is me 0000-0002-5828-8970

Mehmet Ali Eren 0000-0002-3588-2256

Project Number 19251
Publication Date August 28, 2022
Submission Date July 7, 2022
Acceptance Date July 22, 2022
Published in Issue Year 2022 Volume: 19 Issue: 2

Cite

Vancouver Akkafa F, Kenger O, Eren MA. Diyabetik Nefropatili Hastalarda Paraoksonaz 1 Gen Polimorfizmlerinin Araştırılması. Harran Üniversitesi Tıp Fakültesi Dergisi. 2022;19(2):230-8.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty