Association of Angiotensin Converting Enzyme Gene Deletion/Deletion Genotype with Risk of Autosomal Dominant Polycystic Kidney Disease: A Single-center Study from Iranian Azeri Turkish Population
DOI:
https://doi.org/10.61186/Keywords:
ADPKD, ACE, Deletion/DeletionAbstract
Introduction. Autosomal Dominant Polycystic kidney disease (ADPKD) is defined as one of the most common genetic disorders and the cause of kidney failure or end-stage kidney disease (ESKD). Several studies have shown that renin-angiotensin system has an important role in pathogenesis of ADPKD. The aim of this study was to examine the association between the angiotensin converting enzyme (ACE) gene Deletion/Deletion (D/D) polymorphism and risk of ADPKD among Iranian patients from west Azerbaijan province of Iran.
Methods. This case-control study was conducted on 40 patients and 72 controls. Genetic polymorphism of the ACE gene was determined using polymerase chain reaction (PCR) and electrophoresis.
Result. The frequency (frequency%) of ACE gene I/I, I/D, D/D genotypes were 5 (12.5%), 12 (30%), 23 (57.5%) in cases and 16 (22.22%), 30 (41.67%), 26 (36.11%) in controls, respectively. The frequency (frequency%) of ACE gene I and D alleles were 22 (27.5%) and 58 (72.5%) in cases and, 62 (43.06%) and 82 (56.94%) in controls, respectively. Statistical analysis indicated that there were significant differences among the cases and controls regarding ACE gene D/D genotypes (P = .028). The ACE gene D/D genotype was associated with increased ADPKD susceptibility with an OR of 2.39, (95%) CI = (1.09–5.28), and P = .028. But in the case of ACE gene, I/I and I/D genotypes, there were no statistically significant differences between cases and controls (P > .05). Considering allelic comparison, the ACE gene D allele was associated with ADPKD susceptibility with an OR of 1.99, (95%) CI = (1.1–3.6), and P = .021.
Conclusion. Our findings suggest that ACE gene D/D genotype was associated with ADPKD.
Downloads
References
1. Hafizi A, Khatami SR, Galehdari H, Shariati G, Saberi AH, Hamid M. Exon sequencing of PKD1 gene in an Iranian patient with autosomal-dominant polycystic kidney disease. Iran Biomed J. 2014;18(3):143-50.
2. Ha SK, Park CH, Kna JS, et al. Extrarenal manifestations of autosomal dominant polycystic kidney disease. Yonsei Med J. 1997; 38(2):111-6.
3. Stamm ER, Townsend RR, Johnson AM, Garg K, Manco-Johnson M, Gabow PA. Frequency of ovarian cysts in patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1999; 34(1):120-4.
4. Galosi AB, Montironi R, Fabiani A, Lacetera V, Gallé G, Muzzonigro G. Cystic lesions of the prostate gland: an ultrasound classification with pathological correlation. J Urol. 2009; 181(2): 647-57.
5. Belet U, Danaci M, Sarikaya S, et al. Prevalence of epididymal, seminal vesicle, prostate, and testicular cysts in autosomal dominant polycystic kidney disease. Urology. 2002 Jul;60(1):138-41.
6. Pirson Y. Extrarenal manifestations of autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 2010;17(2):173-80.
7. Liu X, Shi X, Xin Q, et al. Identified eleven exon variants in PKD1 and PKD2 genes that altered RNA splicing by minigene assay. BMC Genomics. 2023; 24(1):407.
8. Bagheri M, Makhdoomi K, Taghizadeh Afshari A, Nikibakhsh AA, Abdi Rad I. Identification of Novel Pathogenic PKD2 Variants in Iranian Patients with Autosomal Dominant Polycystic Kidney Disease. Rep Biochem Mol Biol. 2020; 8(4):401-406.
9. Bagheri M, Makhdoomi K, Taghizadeh Afshari A, Nikibakhsh AA, Abdi Rad I. Examining the Role of Polymorphisms in Exon 25 of the PKD1 Gene in the Pathogenesis of Autosomal Dominant Polycystic Kidney Disease in ranian Patients. Rep Biochem Mol Biol. 2019; 8(2):102-110.
10. Zhou X, Torres VE. Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling. Front Mol Biosci. 2022 Sep 2;9:981963.
11. Nowak KL, Edelstein CL. Apoptosis and autophagy in polycystic kidney disease (PKD). Cell Signal. 2020; 68:109518.
12. Roitbak T, Ward CJ, Harris PC, Bacallao R, Ness SA, Wandinger-Ness A. A polycystin-1 multiprotein complex is disrupted in polycystic kidney disease cells. Mol Biol Cell. 2004; 15(3):1334-46.
13. Grosch M, Brunner K, Ilyaskin AV, et al. A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts. J Cell Sci. 2021;134(16): jcs259013.
14. Mehta JK, Kaur G, Buttar HS, et al. Role of the renin-angiotensin system in the pathophysiology of coronary heart disease and heart failure: Diagnostic biomarkers and therapy with drugs and natural products. Front Physiol. 2023; 14: 1034170.
15. Konoshita T, Miyagi K, Onoe T, et al. Effect of ACE gene polymorphism on age at renal death in polycystic kidney disease in Japan. Am J Kidney Dis. 2001; 37(1):113-118.
16. Martyniak A, Tomasik PJ. A New Perspective on the Renin-Angiotensin System. Diagnostics (Basel). 2022; 13(1):16.
17. Mohebbi I, Abdi Rad I, Bagheri M. Association of angiotensin-1-converting enzyme gene variations with silicosis predisposition. Inhal Toxicol. 2010 Nov;22(13):1110-5.
18. Abdi Rad I, Bagheri M. Angiotensin-converting enzyme insertion/deletion gene polymorphism in general population of west Azarbaijan, Iran. Iran J Kidney Dis. 2011; 5(2):86-92.
19. Bagheri M, Abdi Rad I, Omrani MD, Nanbaksh F. Polymorphisms of the angiotensin converting enzyme gene in Iranian Azeri Turkish women with unexplained recurrent pregnancy loss. Hum Fertil (Camb). 2010; 13(2):79-82.
20. Rad IA, Bagheri M, Rahimi-Rad MH. Deletion allele of the ACE gene is not a risk factor for asthma predisposition. Pneumologia. 2011; 60(4): 208-12.
21. Amara A, Mrad M, Sayeh A, et al. The effect of ACE I/D polymorphisms alone and with concomitant risk factors on coronary artery disease. Clin Appl Thromb Hemost. 2018; 24(1):157-163.
22. Aslbahar F, Neamatzadeh H, Tabatabaiee RS, et al. Association of angiotensin-converting enzyme insertion/deletion polymorphism with recurrent pregnancy loss: a meta-analysis of 26 Case-Control Studies. Rev Bras Ginecol Obstet. 2018; 40(10):631-641.
23. Wanic-Kossowska M, Posnik B, Kobelski M, et al. The polymorphism of the ACE gene affects left ventricular hypertrophy and causes disturbances in left ventricular systolic/diastolic function in patients with autosomal dominant polycystic kidney disease. ScientificWorldJournal. 2014; 2014: 707658.
24. Malakoutian T, Madadi B, Ebrahimi A. Evaluation of common polymorphisms of eNOS gene and ACE gene in autosomal dominant polycystic kidney disease patients and their association with HTN and renal failure. J Renal Inj Prev. 2021;10(1):e04.
25. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.
26. Ramanathan G, Elumalai R, Periyasamy S, Lakkakula B. Role of renin-angiotensin-aldosterone system gene polymorphisms and hypertension-induced end-stage renal disease in autosomal dominant polycystic kidney disease. Iran J Kidney Dis. 2014; 8(4):265-77.
27. Ramanathan G, Ghosh S, Elumalai R, Periyasamy S, Lakkakula BV. Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Indian J Med Res. 2016;143(6):748-755.
28. Hian CK, Lee CL, Thomas W. Renin-Angiotensin-Aldosterone System Antagonism and Polycystic Kidney Disease Progression. Nephron. 2016;134(2):59-63.
29. Mizuiri S, Hemmi H, Kumanomidou H, et al. Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression. Kidney Int. 2001 Sep;60(3):1124-30.
30. Pérez-Oller L, Torra R, Badenas C, Milà M, Darnell A. Influence of the ACE gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1999; 34(2):273-8.
31. Lovati E, Richard A, Frey BM, Frey FJ, Ferrari P. Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease. Kidney Int. 2001;60(1):46-54.
32. Su SL, Yang HY, Wu CC, et al. Gene-gene interactions in renin-angiotensin-aldosterone system contributes to end-stage renal disease susceptibility in a Han Chinese population. Scientific World Journal. 2014; 2014: 169798.
33. Buraczynska M, Ksiazek P, Drop A, Zaluska W, Spasiewicz D, Ksiazek A. Genetic polymorphisms of the renin-angiotensin system in end-stage renal disease. Nephrol Dial Transplant. 2006;21(4):979-83.
34. Pereira TV, Nunes AC, Rudnicki M, et al. Influence of ACE I/D gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease: a meta-analysis. Nephrol Dial Transplant. 2006; 21(11):3155-63.
35. Lee KB, Kim UK, Lee CC. Association of the ACE gene polymorphism with the progression of autosomal dominant polycystic kidney disease. J Korean Med Sci. 2000; 15(4):431-5.
36. Schiavello T, Burke V, Bogdanova N, et al. Angiotensin-converting enzyme activity and the ACE Alu polymorphism in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2001; 16(12):2323-7.
37. Omrani MD, Bagheri M. Frequency of CCR5Δ32 Variant in North-West of Iran. Journal of Sciences, Islamic Republic of Iran. 2009; 20(2):105–110.
38. Mohebbi I, Rad IA, Bagheri M. Interleukin-18, interleukin-8, and CXCR2 and the risk of silicosis. Toxicol Ind Health. 2013; 29(9):830-7.
