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2012 | 66 | 2 | 27–33
Article title

Lack of association between single nucleotide polymorphisms of CPA4, LEP and AKR1B1 genes located at the long arm of chromosome 7 (7q31-q35) and chronic kidney disease occurrence and progression

Title variants
Brak związku między polimorfi zmami pojedynczego nukleotydu genów CPA4, LEP oraz AKR1B1 zlokalizowanych na długim ramieniu chromosomu 7 (7q31-q35) a występowaniem i progresją przewlekłej choroby nerek
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BACKGROUND The aim of the study was to investigate the infl uence of single nucleotide polymorphisms (SNPs) of carboxypeptidase A4, CPA4, leptin, LEP and aldo-keto reductase family 1, AKR1B1 genes located at the long arm of chromosome 7 (7q31-q35) on development and progression of chronic kidney disease (CKD). MATERIAL AND METHODS There was an association study by PCR-RFLP method of following SNPs in parent-off spring trios performed: G934T of CPA4 gene, A19G of LEP gene and C-106T of AKR1B gene. 471 subjects, 157 patients with CKD and 314 their biological parents were examined. The patients were divided into 3 groups: diabetic nephropathy due to type 1 diabetes (n = 34), chronic primary glomerulonephritis (n = 70) and chronic inter- stitial nephritis (n = 53). The mode of alleles transmission was determined using the transmission disequilibrium test (TDT). RESULTS There was no association of studied SNPs and CKD occurrence or pro- gression rate of renal function loss. Transmission of alleles of investigated SNPs did not diff er signifi cantly: G934T of CPA4 gene: P = 0.61 in whole group of CKD patients, p = 0.66 in GN group, p = 0.70 – IN group and p = 0.61 in DN one; A19G of LEP gene: p = 0.58, 0.71, 0.78 and 0.49, respectively; C-106T of ALDR1 gene: p = 0.31, 0.47, 0.12 and 0.38, respectively. No impact of examined polymorphisms on the rate of progression of renal function loss was observed. CONCLUSIONS The results, obtained in the study, suggest that the investigated SNPs: G934T of CPA4 gene, A19G of LEP gene and C-106T of AKR1B gene may not play a major role in the development and progression of chronic nephropathies.
WSTĘP Celem badań było zbadanie wpływu polimorfi zmów pojedynczego nukleotydu (SNPs) genów karboksypepsydazy A4, CPA4, leptyny, LEP i reduktazy aldozy, AKR1B1, znajdujących się na długim ramieniu chromosomu 7 (7q31-q35) na rozwój i progresję przewlekłej choroby nerek (PChN). MATERIAŁ I METODY Wykorzystując metodę PCR-RFLP przebadano następujące polimorfizmy: G934T CPA4 genu, A19G LEP i C-106T genu AKR1B. Badaniami objęto 471 osoby: 157 z PChN i 314 ich biologicznych rodziców. Pacjentów podzielono na 3 grupy: z nefropatią cukrzycową w przebiegu cukrzycy typu 1 (DN, n = 34), z przewlekłym pierwotnym kłębuszkowym zapaleniem nerek (GN, n = 70) oraz z przewlekłym śródmiąższowym zapaleniem nerek (IN, n = 53). Tryb przekazywania alleli został oceniony testem nierównowagi przekazywania (Transmission-Disequilibrium Test, TDT). WYNIKI Częstość przekazywania alleli analizowanych SNPs nie odbiegała znacząco od oczekiwanej: G934T CPA4: p = 0,61 w całej grupie badanej, p = 0,66 w grupie GN, p = 0,70 – w grupie IN oraz p = 0,61 w grupie DN; A19G LEP: p = 0,58; 0,71; 0,78 i 0,49, odpowiednio; C-106T genu ALDR1: p = 0,31; 0,47; 0,12 i 0,38, odpowiednio. Nie zaobserwowano żadnego wpływu badanych polimorfi zmów na szybkość utraty funkcji nerek. WNIOSKI Uzyskane w badaniu wyniki wskazują, że badane SNPs: G934T genu CPA4, A19G LEP i C-106T genu AKR1B nie odgrywają istotnej roli w rozwoju i progresji przewlekłych nefropatii.

Physical description
  • Department of Internal Medicine, Diabetology and Nephrology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice
  • Department of Internal Medicine, Diabetology and Nephrology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice
  • Department of Internal Medicine, Diabetology and Nephrology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice
  • Department of Internal Medicine, Diabetology and Nephrology School of Medicine with the Division of Dentistry in Zabrze Medical University of Silesia in Katowice ul. 3 Maja 13/15 41-800 Zabrze, Poland tel. 48 32 371 25 11 fax 48 32 271 46 17,
  • Department of Internal Medicine, Diabetology and Nephrology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice
  • 1. Collins A.J., Foley R.N., Chavers B. et al. United States Renal Data System 2011 Annual Data Report: Atlas of chronic kidney disease & end-stage renal disease in the United States. Am. J. Kidney Dis. 2012; 59(1 Suppl 1): A7, e1–420.
  • 2. Coresh J., Selvin E., Stevens L.A. Preva- lence of Chronic Kidney Disease in the United States. JAMA 2007; 298: 2038– –2047.
  • 3. Satko S.G., Sedor J.R., Iyengar S.K., Freed- man B.I. Familial clustering of chronic kid- ney disease. Sem. Dial. 2007; 20: 229–236.
  • 4. Cargill M., Altshuler D., Ireland J. et al. Characterization of single-nucleotide poly- morphisms in coding regions of human genes. Nat. Genet. 1999; 22: 231–238.
  • 5. Spielman R.S., Ewens W.J. A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am. J. Hum. Genet. 1998; 62: 450–458.
  • 6. Spielman R.S., McGinnis R.E., Ewens W.J. Transmission test for linkage disequi- librium: the insulin gene region and insu- lin-dependent diabetes mellitus (IDDM). Am. J. Hum. Genet. 1993; 52: 506–516.
  • 7. Poggio E.D., Wang X., Greene T., Van Lente F., Hall P.M. Performance of the Modifi cation of Diet in Renal Disease and Cockcroft-Gault Equations in the Estima- tion of GFR in Health and in Chronic Kidney Disease. J. Am. Soc. Nephrol. 2005, 16: 459–466.
  • 8. Schwartz G.J., Haycock G.B., Edelmann C.M., Spitzer A. A simple estimate of glomerular fi ltration rate in children de- rived from body length and plasma creati- nine. Pediatrics 1976; 58: 259–263.
  • 9. Levey A.S., Eckardt K.U., Tsukamoto Y. et al. Defi nition and classifi cation of chron- ic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005; 67: 2089–2100.
  • 10. Laird N.M., Lange Ch. Family-based designs in the age of large-scale gene-as- sociation studies. Nat. Rev. Gen. 2006; 7: 385–394.
  • 11. Placha G., Canani L.H., Warram J.H., Krolewski A.S. Evidence for diff erent sus- ceptibility genes for proteinuria and ESRD in type 2 diabetes. Adv. Chronic Kidney Dis. 2005; 12 (2): 155–169.
  • 12. Wei S., Segura S., Vendrell J. et al. Iden- tifi cation and characterization of three members of the human metallo-carbox- ypeptidase gene family. J. Biol. Chem. 2002; 277: 14954–14964.
  • 13. Huang H., Reed Ch.P. i wsp. Car- boxypeptidase A3 (CPA3): a novel gene highly induced by histone deacetylase in- hibitors during diff erentiation of prostate epithelial cancer cells. Cancer Res. 1999; 59: 2981–2988.
  • 14. Pallares I., Bonet R., Garcia-Castellanos R. i wsp. Structure of human carboxy- peptidase A4 with its endogenous pro- tein inhibitor, latexin. PNAS. 2005; 102, 11: 3978–3983.
  • 15. Hutchison F.N., Martin V.I. Eff ects of modulation of renal kallikreiny-kinin system in the nephrotic syndrome. Am. J. Physiol. 1990; 258: F1237–F1244.
  • 16. Yu H., Bowden D.W., Spray B.J., Rich S.S., Freedman B.I. Identifi cation of human plasma kallikrein gene polymorphism and evaluation of their role in end-stage renal disease. Hypertension 1998; 31: 906–911.
  • 17. Mathew A.V., Okada S., Sharma K. Obesity related kidney disease. Curr. Dia- betes Rev. 2011; 7: 41–49.
  • 18. Papafraghaki D.K., Tolis G. Obesity and renal disease: a possible role of leptin. Hor- mones 2005; 4: 90–95.
  • 19. Briley L.P., Szczech L.A. Leptin and re- nal disease. Sem. Dial. 2006; 19: 54–59.
  • 20. Praga M., Hernandez E., Morales E. et al. Clinical features and long-term out- come of obesity-associated focal segmental glomerulosclerosis. Nephrol. Dial. Trans- plant. 2001; 16: 1790–1798.
  • 21. Saxena A.K., Chopra R. Renal risk of an emerging „epidemic” of obesity: the role of adipocyte-derived factors. Nephrol. Dial. Transplant. 2004; 33, 1: 11–20.
  • 22. Tutle K.R.: Renal manifestations of the metabolic syndrome. Nephrol. Dial. Trans- plant. 2005; 20: 861–864.
  • 23. Han D.C., Isono M., Chen S. et al. Lep- tin stimulates type I collagen production in db/db mesangial cells: glucose uptake and TGF-beta type II receptor expression. Kid- ney Int. 2001; 59: 1315–1323.
  • 24. Wolf G., Chen S., Han D.Ch., Ziyadeh F.N. Leptin and renal disease. Am. J. Kid- ney Dis. 2002; 39,1: 1–11.
  • 25. Wolf G., Hamann A., Han D.C. et al. Leptin stimulates proliferation and TGF-􀈕 expression in renal glomerular endothelial cells: potential role in glomerulosclerosis. Kidney Int. 1999; 56: 860–872.
  • 26. Carlyle M., Jones O.B., Kuo J.J., Hall J.E. Chronic cardiovascular and renal actions of leptin. Role of adrenergic activity. Hy- pertension 2002; 39 [part 2]: 496–501.
  • 27. Kuo J.J., Jones O.B., Hall J.E. Inhibition of NO synthesis enhances chronic cardio- vascular and renal actions of leptin. Hy- pertension 2001; 37 [part 2]: 670–676.
  • 28. Granier C., Makni K., Molina L., Jar- din-Watelet B., Ayadi H., Jarraya F.: Gene and protein markers of diabetic neph- ropathy. Nephrol. Dial. Transplant. 2008; 23: 792–799.
  • 29. Shah V.O., Scavini M., Nikolic J. et al. Z-2 microsatellite allele is linked to in- creased expression of the aldose reductase gene in diabetic nephropathy. J. Clin. En- docrinol. Metab. 1998; 83: 2886–2891.
  • 30. Makiishi T., Araki S., Koya D., Maeda S., Kashiwagi A., Haneda M. C-106T polymorphism of AKR1B1 is associated with diabetic nephropathy and erythro- cyte aldose reductase kontent in Japanese subjects with type 2 diabetes mellitus. Am. J. Kidney Dis. 2003; 42: 943–951.
  • 31. Moczulski D.K., Scott L., Antonellis A. et al. Aldose reductase gene polymorphisms and susceptibility to diabetic nephropathy in Type 1 diabetes mellitus. Diabet. Med. 2000; 17: 111–118.
  • 32. Neamat-Allah M., Feeney S.A., Savage D.A. et al. Analysis of the association be- tween diabetic nephropathy and polymor- phism in the aldose reductase gene in type 1 and type 2 diabetes mellitus. Diabet. Med. 2001; 18: 906–914.
  • 33. Wang Y., Ng M.C., Lee S.C. et al. Phe- notypic heterogeneity and associations of two aldose reductase gene polymor- phisms with nephropathy and retinopathy in type 2 diabetes. Diabetes Care 2003; 26: 2410–2415.
  • 34. Dyer P.H., Chowdhury T.A., Drons- fi eld M.J., Dunger D., Barnett A.H., Bain S.C. The 5’-end polymorphism of the al- dose reductase gene is not associated with diabetic nephropathy in Caucasian type I diabetic patients. Diabetologia 1999; 42: 1030–1031.
  • 35. Ewens K.G., George R.A., Sharma K., Ziyadeh F.N., Spielman R.S. Assessment of 115 candidate genes for diabetic neph- ropathy by transmission/disequilibrium test. Diabetes. 2005; 54: 3305–3318.
  • 36. Wolford J.K., Yeatts K.A., Red Eagle A.R., Nelson R.G., Knowler W.C., Hanson R.L. Variants in the gene encoding aldose reductase (AKR1B1) and diabetic neph- ropathy in American Indians. Diabet. Med. 2006; 23: 367–376.
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