Background: Heat shock proteins (HSPs) are expressed by cells in response to various environmental stresses. A single-nucleotide polymorphism A+1267G of the HSPA1B gene affects the expression of HSP70-2, with the A allele being protective against inflammatory conditions. We investigated the relation between the HSP A+1267G polymorphism and the clinical outcomes of Chinese peritoneal dialysis (PD) patients. Methods: We studied 347 new PD cases (181 males, age 56.6 ± 13.7 years). Genotyping was done by standard methods. Patients were followed for 40.5 ± 20.7 months for survival analysis. Results: For the entire cohort, there was no difference in the 5-year survival between genotype groups. However, there was a significant interaction between HSP polymorphism and diabetic status on the cardiovascular event-free survival. In patients without pre-existing diabetes, 5-year cardiovascular event-free survival of the GG/AG genotype group was significantly better than that of the AA genotype group (57.2 vs. 32.1%, p = 0.011). Conclusion: The G allele of the HSP70-2 A+1267G polymorphism confers survival advantages in non-diabetic PD patients. The role of HSP in the pathogenesis of cardiovascular disease in renal failure patients needs further investigation.

1.
Yu AWY, Chau KF, Ho YW, Li PKT: Development of the ‘peritoneal dialysis first' model in Hong Kong. Perit Dial Int 2007;27:S53-S55.
2.
Li PKT, Szeto CC: Success of the peritoneal dialysis programme in Hong Kong. Nephrol Dial Transplant 2008;23:1475-1478.
3.
Li PKT, Chow KM: The clinical and epidemiological aspects of vascular mortality in chronic peritoneal dialysis patients. Perit Dial Int 2005;25:S80-S83.
4.
Krediet RT, Balafa O: Cardiovascular risk in the peritoneal dialysis patient. Nat Rev Nephrol 2010;6:451-460.
5.
Ducloux D, Bresson-Vautrin C, Kribs M, Abdelfatah A, Chalopin JM: C-reactive protein and cardiovascular disease in peritoneal dialysis patients. Kidney Int 2002;62:1417-1422.
6.
Cangemi R, Angelico F, Loffredo L, Del Ben M, Pignatelli P, Martini A, Violi F: Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: effect of ascorbic acid. Free Radic Biol Med 2007;43:853-859.
7.
Stephens JW, Bain SC, Humphries SE: Gene-environment interaction and oxidative stress in cardiovascular disease. Atherosclerosis 2008;200:229-238.
8.
Heistad DD, Wakisaka Y, Miller J, Chu Y, Pena-Silva R: Novel aspects of oxidative stress in cardiovascular diseases. Circ J 2009;73:201-207.
9.
Choi HY, Lee JE, Han SH, Yoo TH, Kim BS, Park HC, Kang SW, Choi KH, Ha SK, Lee HY, Han DS: Association of inflammation and protein-energy wasting with endothelial dysfunction in peritoneal dialysis patients. Nephrol Dial Transplant 2010;25:1266-1271.
10.
Ha H, Yu MR, Lee HB: High glucose-induced PKC activation mediates TGF-beta 1 and fibronectin synthesis by peritoneal mesothelial cells. Kidney Int 2001;59:463-470.
11.
Welten AG, Schalkwijk CG, ter Wee PM, Meijer S, van den Born J, Beelen RJ: Single exposure of mesothelial cells to glucose degradation products (GDPs) yields early advanced glycation end-products (AGEs) and a proinflammatory response. Perit Dial Int 2003;23:213-221.
12.
Inagi R, Miyata T, Yamamoto T, Suzuki D, Urakami K, Saito A, van Ypersele de Strihou C, Kurokawa K: Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells: role in the functional and morphological alterations of peritoneal membranes in peritoneal dialysis. FEBS Lett 1999;463:260-264.
13.
Boulanger E, Wautier MP, Wautier JL, Boval B, Panis Y, Wernert N, Danze PM, Dequiedt P: AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression. Kidney Int 2002;61:148-156.
14.
Feder ME, Hofmann GE: Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol 1999;61:243-282.
15.
Aufricht C: Heat-shock protein 70: molecular supertool? Pediatr Nephrol 2005;20:707-713.
16.
Meimaridou E, Gooljar SB, Chapple JP: From hatching to dispatching: the multiple cellular roles of the Hsp70 molecular chaperone machinery. J Mol Endocrinol 2009;42:1-9.
17.
Mayer MP: Gymnastics of molecular chaperones. Mol Cell 2010;39:321-331.
18.
Nagata K, Saga S, Yamada KM: A major collagen-binding protein of chick embryo fibroblasts is a novel heat shock protein. J Cell Biol 1986;103:223-229.
19.
Trautinger F, Kindås-Mügge I, Knobler RM, Hönigsmann H: Stress proteins in the cellular response to ultraviolet radiation. J Photochem Photobiol B 1996;35:141-148.
20.
Jonak C, Klosner G, Trautinger F: Significance of heat shock proteins in the skin upon UV exposure. Front Biosci 2009;14:4758-4768.
21.
Jones Q, Voegeli TS, Li G, Chen Y, Currie RW: Heat shock proteins protect against ischemia and inflammation through multiple mechanisms. Inflamm Allergy Drug Targets 2011;10:247-259.
22.
Kalmar B, Greensmith L: Induction of heat shock proteins for protection against oxidative stress. Adv Drug Deliv Rev 2009;61:310-318.
23.
Beyersmann D, Hechtenberg S: Cadmium, gene regulation, and cellular signalling in mammalian cells. Toxicol Appl Pharmacol 1997;144:247-261.
24.
Razzaque MS, Taguchi T: Involvement of stress proteins in renal diseases. Contrib Nephrol 2005;148:1-7.
25.
Yabunaka N, Ohtsuka Y, Watanabe I, Noro H, Fujisawa H, Agishi Y: Elevated levels of heat-shock protein 70 (HSP70) in the mononuclear cells of patients with non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1995;30:143-147.
26.
Genth-Zotz S, Bolger AP, Kalra PR, von Haehling S, Doehner W, Coats AJ, Volk HD, Anker SD: Heat shock protein 70 in patients with chronic heart failure: relation to disease severity and survival. Int J Cardiol 2004;96:397-401.
27.
Barutta F, Pinach S, Giunti S, Vittone F, Forbes JM, Chiarle R, Arnstein M, Perin PC, Camussi G, Cooper ME, Gruden G: Heat shock protein expression in diabetic nephropathy. Am J Physiol Renal Physiol 2008;295:F1817-F1824.
28.
Calabrese V, Cornelius C, Leso V, Trovato-Salinaro A, Ventimiglia B, Cavallaro M, Scuto M, Rizza S, Zanoli L, Neri S, Castellino P: Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes. Biochim Biophys Acta 2012;1822:729-736.
29.
Shioshita K, Miyazaki M, Ozono Y, Abe K, Taura K, Harada T, Koji T, Taguchi T, Kohno S: Expression of heat shock proteins 47 and 70 in the peritoneum of patients on continuous ambulatory peritoneal dialysis. Kidney Int 2000;57:619-631.
30.
Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetham ME, Chen B, Hightower LE: Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 2009;14:105-111.
31.
Pociot F, Rønningen KS, Nerup J: 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 1993;38:491-495.
32.
Lu HQ, Wang YZ, Sun PH, Liang SP, Li J, Wang XL, Xu D, Yao W, Wu YM, Zhou F: Effects of heat shock protein 70-2 gene polymorphisms on the transcription of HSP 70-2 mRNA and the translation of HSP 70 protein in lung cancer. Zhonghua Yu Fang Yi Xue Za Zhi 2012;46:452-455.
33.
Giacconi R, Caruso C, Lio D, Muti E, Cipriano C, Saba V, Boccoli G, Gasparini N, Malavolta M, Mocchegiani E: 1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients. Mech Ageing Dev 2005;126:866-873.
34.
Schroeder S, Reck M, Lehmann LE, Book M, Hoeft A, Stüber F: The Pstl polymorphism of the endotoxin-inducible heat-shock protein 70-2 gene does not affect messenger RNA level in human whole-blood cultures. Intensive Care Med 2000;26:1139-1143.
35.
Esaki M, Furuse M, Matsumoto T, Aoyagi K, Jo Y, Yamagata H, Nakano H, Fujishima M: Polymorphism of heat-shock protein gene HSP70-2 in Crohn disease: possible genetic marker for two forms of Crohn disease. Scand J Gastroenterol 1999;34:703-707.
36.
Klausz G, Molnár T, Nagy F, Gyulai Z, Boda K, Lonovics J, Mándi Y: Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn's disease. Scand J Gastroenterol 2005;40:1197-1204.
37.
Zouari Bouassida K, Chouchane L, Jellouli K, Chérif S, Haddad S, Gabbouj S, Danguir J: Polymorphism of stress protein HSP70-2 gene in Tunisians: susceptibility implications in type 2 diabetes and obesity. Diabetes Metab 2004;30:175-180.
38.
Balog A, Gyulai Z, Boros LG, Farkas G, Takács T, Lonovics J, Mándi Y: Polymorphism of the TNF-alpha, HSP70-2, and CD14 genes increases susceptibility to severe acute pancreatitis. Pancreas 2005;30:e46-e50.
39.
Buraczynska M, Swatowski A, Buraczynska K, Dragan M, Ksiazek A: Heat-shock protein gene polymorphisms and the risk of nephropathy in patients with type 2 diabetes. Clin Sci (Lond) 2009;116:81-86.
40.
Vargas-Alarcón G, Londoño JD, Hernández-Pacheco G, Gamboa R, Castillo E, Pacheco-Tena C, Cardiel MH, Granados J, Burgos-Vargas R: Heat shock protein 70 gene polymorphisms in Mexican patients with spondyloarthropathies. Ann Rheum Dis 2002;61:48-51.
41.
Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH: A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients. Am J Kidney Dis 2001;38:1251-1263.
42.
Enia G, Sicus C, Alati G, Zoccali C: Subjective global assessment of nutrition in dialysis patients. Nephrol Dial Transplant 1993;8:1094-1098.
43.
González-Ramos M, Calleros L, López-Ongil S, Raoch V, Griera M, Rodríguez-Puyol M, de Frutos S, Rodríguez-Puyol D: HSP70 increases extracellular matrix production by human vascular smooth muscle through TGF-β1 up-regulation. Int J Biochem Cell Biol 2013;45:232-242.
44.
Leng X, Wang X, Pang W, Zhan R, Zhang Z, Wang L, Gao X, Qian L: Evidence of a role for both anti-Hsp70 antibody and endothelial surface membrane Hsp70 in atherosclerosis. Cell Stress Chaperones 2013;18:483-493.
45.
Figueredo A, Ibarra JL, Rodriguez A, Molino AM, Gomez-de la Concha E, Fernandez-Cruz A, Patiño R: Increased serum levels of IgA antibodies to hsp70 protein in patients with diabetes mellitus: their relationship with vascular complications. Clin Immunol Immunopathol 1996;79:252-255.
46.
Nakhjavani M, Morteza A, Khajeali L, Esteghamati A, Khalilzadeh O, Asgarani F, Outeiro TF: Increased serum HSP70 levels are associated with the duration of diabetes. Cell Stress Chaperones 2010;15:959-964.
47.
Lo WK: Serum parameters, inflammation, renal function and patient outcome. Contrib Nephrol 2006;150:152-155.
48.
Fouque D, Kalantar-Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, Franch H, Guarnieri G, Ikizler TA, Kaysen G, Lindholm B, Massy Z, Mitch W, Pineda E, Stenvinkel P, Treviño-Becerra A, Wanner C: A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int 2008;73:391-398.
49.
De Mutsert R, Grootendorst DC, Indemans F, Boeschoten EW, Krediet RT, Dekker FW; Netherlands Cooperative Study on the Adequacy of Dialysis-II Study Group: Association between serum albumin and mortality in dialysis patients is partly explained by inflammation, and not by malnutrition. J Ren Nutr 2009;19:127-135.
50.
Leinig CE, Moraes T, Ribeiro S, Riella MC, Olandoski M, Martins C, Pecoits-Filho R: Predictive value of malnutrition markers for mortality in peritoneal dialysis patients. J Ren Nutr 2011;21:176-183.
51.
Mehrotra R, Duong U, Jiwakanon S, Kovesdy CP, Moran J, Kopple JD, Kalantar-Zadeh K: Serum albumin as a predictor of mortality in peritoneal dialysis: comparisons with hemodialysis. Am J Kidney Dis 2011;58:418-428.
52.
Kim do K, Lee SM, Son YK, Kim SE, Kim KH, An WS: Factors influencing survival according to elapsed time in peritoneal dialysis patients. Ren Fail 2012;34:559-565.
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