Abstract
Heat shock protein (HSP)70 plays an important role in the ischemic tolerance of fetal and neonatal kidney. We have investigated the association of genetic polymorphisms of the constitutive HSP70 (HSP73) and the inducible HSP70 (HSP72) encoding genes with the risk of acute renal failure (ARF) in very low birth weight (VLBW) neonates. Thirty-seven VLBW neonates with ARF and 93 VLBW neonates without ARF were enrolled in the study. The presence of HSP72 (1267)AG and HSP73 (190)GC polymorphism was analyzed from dried blood samples by PCR and restriction length fragment polymorphism. Allelic prevalence was related to reference values obtained in 131 healthy adults. Stepwise binary logistic regression was applied to determine the independent effect of the established risk factors to the development of ARF. Sixteen of 37 VLBW neonates with ARF and 18 of 93 VLBW neonates without ARF were homozygous for HSP72 (1267)G allele (p ≤ 0.01). The association between HSP72 (1267)GG genotype and ARF remained at the level of significance (p = 0.05) when it was adjusted for established risk factors of neonatal ARF. Prevalence of HSP72 (1267)GG was also higher in VLBW neonates than in the reference population (p < 0.05) and in VLBW neonates with infant respiratory distress syndrome than in those without (p < 0.001). We found that in VLBW neonates carrying HSP72 (1267)GG genetic variation, which is associated with low inducibility of HSP72, the risk of ARF was increased. Therefore, VLBW neonates with (1267)GG might express less HSP72 and might be less protected against ARF.
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Abbreviations
- HSP:
-
heat shock protein
- ARF:
-
acute renal failure
- VLBW:
-
very low birth weight
- NEC:
-
necrotizing enterocolitis
- IRDS:
-
infant respiratory distress syndrome
- PDA:
-
patent ductus arteriosus
References
Tóth-Heyn P, Drukker A, Guignard JP 2000 The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy. Pediatr Nephrol 14: 227–239
Kelly KJ, Molitoris BA 2000 Acute renal failure in the new millennium: time to consider combination therapy. Semin Nephrol 20: 4–19
Modi N 1999 Disorders of the kidney and urinary tract. In: Rennie JM, Roberton NR (eds) Textbook of Neonatology. Churchill-Livingston, Edinburgh, pp 1009–1037.
Molitoris BA 1991 New insights into the cell biology of ischemic acute renal failure. J Am Soc Nephrol 1: 1263–1270
Beck FX, Neuhofer W, Müller E 2000 Molecular chaperones in the kidney: distribution, putative roles and regulation. Am J Physiol 279: F203–F215
Ozer EA, Yilmaz O, Akhisaroglu M, Tuna B, Bakiler AR, Ozer E 2002 Heat shock protein 70 expression in neonatal rats after hypoxic stress. J Matern Fetal Neonatal Med 12: 112–117
Gaudio KM, Thulin G, Mann A, Kashgarian M, Siegel NJ 1998 Role of heat stress response in the tolerance of immature renal tubules to anoxia. Am J Physiol 274: F1029–F1036
Vicencio A, Bidmon B, Ryu J, Reidy K, Thulin G, Mann A, Gaudio KM, Kashgarian M, Siegel NJ 2003 Developmental expression of HSP-72 and ischemic tolerance of the immature kidney. Pediatr Nephrol 18: 85–91
Pociot F, Ronningen KS, Nerup J 1993 Polymorphic analysis of the human MHC-linked heat shock protein 70 (HSP70–2) and HSP70-Hom genes in insulin-dependent diabetes mellitus (IDDM). Scand J Immunol 38: 491–495
Favatier F, Bornman L, Hightower LE, Gunther E, Polla BS 1997 Variation in HSP gene expression and HSP polymorphism: do they contribute to differential disease susceptibility and stress tolerance?. Cell Stress Chaperones 2: 141–155
Bolla MK, Miller GJ, Yellon DM, Evans A, Luc G, Cambou JP, Arveiler D, Cambien F, Latchman DS, Humphries SE, Day IN 1998 Analysis of the association of a heat shock protein 70–1 gene promoter polymorphism with myocardial infarction and coronary risk traits. Dis Markers 13: 227–235
Zee RY, Bates D, Ridker PM 2002 A prospective evaluation of the heat shock protein 70 gene polymorphisms and the risk of stroke. Thromb Haemost 87: 622–625
Nobilis A, Kocsis I, Tóth-Heyn P, Treszl A, Schuler A, Tulassay T, Vásárhelyi B 2001 Variance of ACE, and AT1 receptor gene do not influence the risk of neonatal acute renal failure. Pediatr Nephrol 16: 1063–1066
Miller SA, Dykes DD, Polesky HE 1988 A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 44: 628–632
Van Why SK, Hildebrandt F, Ardito T, Mann AS, Siegel NJ, Kashgarian M 1992 Induction and intracellular localization of HSP-72 after renal ischemia. Am J Physiol 263: F769–F775
Kelly KJ, Baird NR, Greene AL 2001 Induction of stress response proteins and experimental renal ischemia/reperfusion. Kidney Int 59: 1798–1802
Luft JC, Dix DJ 1999 HsP 70 expression and function during embryogenesis. Cell Stress Chaperones 4: 162–170
Schulte CM, Dignass AU, Goebell H, Roher HD, Schulte KM 2000 Genetic factors determine extent of bone loss in inflammatory bowel disease. Gastroenterology 119: 909–920
Mestiri S, Bouaouina N, Ahmed SB, Khedhaier A, Jrad BB, Remadi S, Chouchane L 2001 Genetic variation in the tumor necrosis factor-alpha promoter region and in the stress protein hsp70–2: susceptibility and prognostic implications in breast carcinoma. Cancer 91: 672–678
Schroder O, Schulte KM, Ostermann P, Roher HD, Ekkernkamp A, Laun RA 2003 Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury. Crit Care Med 31: 73–79
David JC, Tanguay RM, Grongnet JF 2001 Perinatal expression of heat shock proteins HSC 70 and HSP 70 in neural and non-neural tissues of the piglet. Brain Res Dev Brain Res 128: 91–99
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The authors thank Mária Bernáth for technical assistance.
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Supported by OTKA Grant F032024-T34605 and by K+F (Hungarian Scientific Education) Grant 0134/2001.
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Fekete, A., Treszl, A., Tóth-Heyn, P. et al. Association between Heat Shock Protein 72 Gene Polymorphism and Acute Renal Failure in Premature Neonates. Pediatr Res 54, 452–455 (2003). https://doi.org/10.1203/01.PDR.0000083024.05819.47
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DOI: https://doi.org/10.1203/01.PDR.0000083024.05819.47
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