Abstract
Background
Kidney disease is a serious public health problem worldwide. It is the fifth top-ranking cause of death in Egypt, causing approximately 3.98% of all deaths. This study’s objective was to examine whether an association exists between leptin (− 2548G/A) and uncoupling protein-2 45 bp I/D genes, individually and collectively, in CKD and progression to ESRD.
Methods
One hundred patients (69 males, 31 females) aged (47.1 ± 16.11 years) with ESRD, 40 patients (19 males, 21 females) aged (43.15 ± 10.00 years with CKD, and 50 healthy controls (23 males, 27 females) aged (37.84 ± 1.95 years) were enrolled. Polymerase chain reaction (PCR) was employed to measure variation in gene expression among the study groups. The frequency of single nucleotide polymorphisms (SNP) genotypes were identified in controls, CKD and ESRD patients.
Results
Leptin genotypes were associated with lower CKD incidence in control versus study subjects (95% CI = (0.08–0.63), P = 0.01) with risk value equal to 0.22 < 1, G/A genotype was significantly lower in CKD than ESRD groups. There was no correlation between UCP-2 I/D genotype and CKD (P = 0.27). There was no correlation between the UCP-2 gene and the progression to ESRD.
Conclusions
This study suggests that, Leptin − 2548G/A gene may be a promising marker for early detection of ESRD in Egyptian patients. G/A genotype might inhibit the development of CKD to ESRD.
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References
Webster AC, Nagler EV, Morton RL, Masson P (2017) Chronic kidney disease. The Lancet 389(10075):1238–1252
Bronze-da-Rocha E, Santos-Silva A (2018) Neutrophil elastase inhibitors and chronic kidney disease. Int J Biol Sci 14(10):1343–1360. https://doi.org/10.7150/ijbs.26111
Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382(9888):260–272. https://doi.org/10.1016/S0140-6736(13)60687-X
Tripathi G, Sharma RK, Baburaj VP, Sankhwar SN, Jafar T, Agrawal S (2008) Genetic risk factors for renal failure among north Indian ESRD patients. Clin Biochem 41(7–8):525–531
Gong D-W, Bi S, Pratley RE, Weintraub BD (1996) Genomic structure and promoter analysis of the human obese gene. J Biol Chem 271(8):3971–3974
Thieme K, Oliveira-Souza M (2015) Renal hemodynamic and morphological changes after 7 and 28 days of leptin treatment: the participation of angiotensin II via the AT1 receptor. PLoS ONE 10(3):e0122265. https://doi.org/10.1371/journal.pone.0122265
DiSilvestro DJ, Melgar-Bermudez E, Yasmeen R, Fadda P, Lee LJ, Kalyanasundaram A, Gilor CL, Ziouzenkova O (2016) Leptin Production by encapsulated adipocytes increases brown fat, decreases resistin, and improves glucose intolerance in obese mice. PLoS ONE 11(4):e0153198. https://doi.org/10.1371/journal.pone.0153198
EL-Said A, AbdeL-Aziz A, AL-Sayed Ebead B (2013) Glutathione S-transferase enzyme (GSTT1 and GSTM1) gene polymorphisms and oxidative stress in Egyptian patients with end stage renal disease. Int J Biol Chem 3(4):315−327
Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, Bouillaud F, Seldin MF, Surwit RS, Ricquier D, Warden CH (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 15(3):269–272. https://doi.org/10.1038/ng0397-269
Pierelli G, Stanzione R, Forte M, Migliarino S, Perelli M, Volpe M, Rubattu S (2017) Uncoupling protein 2: a key player and a potential therapeutic target in vascular diseases. Oxidative Med Cell Longevit 2017:7348372. https://doi.org/10.1155/2017/7348372
De Miguel C, Hamrick WC, Jagarlamudi S, Assico L, Jose PA, Cuevas S (2017) Role of UCP2 on mitochondrial dysfunction in the renal oxidative stress-mediated hypertension associated with DJ-1 depletion. FASEB J 31 (1_supplement):859.856–859.856
Levey AS, Coresh J, Greene T, Stevens LA, Zhang Y, Hendriksen S, Kusek JW, Van Lente F (2006) Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145(4):247–254
Le Stunff C, Le Bihan C, Schork NJ, Bougnères P (2000) A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls. Diabetes 49(12):2196–2200
Hashemi M, Rezaei H, Kaykhaei M-A, Taheri M (2014) A 45-bp insertion/deletion polymorphism of UCP2 gene is associated with metabolic syndrome. J Diabetes Metab Disord 13(1):12
Yuen NK, Ananthakrishnan S, Campbell MJ (2016) Hyperparathyroidism of renal disease. The Permanente Journal 20 (3)
Gal-Moscovici A, Sprague SM (2007) Bone health in chronic kidney disease-mineral and bone disease. Adv Chronic Kidney Dis 14(1):27–36. https://doi.org/10.1053/j.ackd.2006.10.010
McClellan W, Aronoff SL, Bolton WK, Hood S, Lorber DL, Tang KL, Tse TF, Wasserman B, Leiserowitz M (2004) The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin 20(9):1501–1510. https://doi.org/10.1185/030079904X2763
Fabrizi F, Lunghi G, Finazzi S, Colucci P, Pagano A, Ponticelli C, Locatelli F (2001) Decreased serum aminotransferase activity in patients with chronic renal failure: impact on the detection of viral hepatitis. Am J Kidney Dis 38(5):1009–1015. https://doi.org/10.1053/ajkd.2001.28590
Masuda T, Ohara K, Nagayama I, Matsuoka R, Murakami T, Nakagawa S, Oka K, Asakura M, Igarashi Y, Fukaya Y, Miyazawa Y, Maeshima A, Akimoto T, Saito O, Nagata D (2019) Impact of serum albumin levels on the body fluid response to tolvaptan in chronic kidney disease patients. Int Urol Nephrol 51(9):1623–1629. https://doi.org/10.1007/s11255-019-02180-8
Brennan AM, Mantzoros CS (2007) Leptin and adiponectin: their role in diabetes. Curr DiabRep 7(1):1–2
Okpechi IG, Pascoe MD, Swanepoel CR, Rayner BL (2007) Microalbuminuria and the metabolic syndrome in non-diabetic black Africans. Diabetes Vasc Dis Res 4(4):365–367. https://doi.org/10.3132/dvdr.2007.066
Okpechi IG, Rayner BL, Van Der Merwe L, Mayosi BM, Adeyemo A, Tiffin N, Ramesar R (2010) Genetic variation at selected SNPs in the leptin gene and association of alleles with markers of kidney disease in a Xhosa population of South Africa. PLoS ONE 5(2):e9086
Sharma R, Agrawal S, Saxena A, Pandey M, Sharma RK (2013) Association of genetic variants of ghrelin, leptin and UCP2 with malnutrition inflammation syndrome and survival in end-stage renal disease patients. Genes Nutr 8(6):611–621. https://doi.org/10.1007/s12263-013-0353-7
Briley LP, Szczech LA Leptin and renal disease. In: Seminars in Dialysis, 2006. vol 1. Wiley Online Library, pp 54–59
Donadelli M, Dando I, Fiorini C, Palmieri M (2014) UCP2, a mitochondrial protein regulated at multiple levels. Cell Mol Life Sci 71(7):1171–1190
Nigro M, De Sanctis C, Formisano P, Stanzione R, Forte M, Capasso G, Gigliotti G, Rubattu S, Viggiano D (2018) Cellular and subcellular localization of uncoupling protein 2 in the human kidney. J Mol Histol 49(4):437–445
Jia JJ, Zhang X, Ge CR, Jois M (2009) The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes. Obes Rev 10(5):519–526
Rudofsky G, Schrödter A, Voron'ko O, Schlotterer A, Humpert P, Tafel J, Nawroth P, Bierhaus A, Hamann A (2007) Promoter polymorphisms of UCP1, UCP2, and UCP3 are not associated with diabetic microvascular complications in type 2 diabetes. Horm Metab Res 39(04):306–309
Avesani CM, Kamimura MA, Utaka S, Pecoits-Filho R, Nordfors L, Stenvinkel P, Lindholm B, Draibe SA, Cuppari L (2008) Is UCP2 gene polymorphism associated with decreased resting energy expenditure in nondialyzed chronic kidney disease patients? J Renal Nutr 18(6):489–494
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EG1: study concept, drafting, design, statistical analysis, and approval of the manuscript. DS2: study concept, drafting, design, and approval of the manuscript. AE3: study concepting, drafting, design, and approval of the manuscript. MA: data collection and approval of the manuscript.
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Voluntary informed consent was given by all participants. Privacy and confidentiality of all participants' personal, clinical, and laboratory data were maintained throughout the study. This work was carried out in accordance with the rules of the Declaration of Helsinki
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Ghazaly, E.A., EL-Saeed, A.M., Abdelsalam, M. et al. Potential protective effect of leptin and uncoupling protein-2 genes polymorphism in Egyptian patients with chronic kidney disease. Int Urol Nephrol 52, 2153–2160 (2020). https://doi.org/10.1007/s11255-020-02567-y
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DOI: https://doi.org/10.1007/s11255-020-02567-y