RESEARCH PAPER
No associations between rs2030712 and rs7456421 single nucleotide polymorphisms of HIPK2 gene and prevalence of chronic kidney disease. Results of a family-based study
1
Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Katowice, Poland
2
Department of Paediatric Nephrology, Medical University, Wrocław, Poland
3
Institute of Computer Science, Silesian University of Technology, Gliwice, Poland
Ann Agric Environ Med. 2013;20(1):131-134
KEYWORDS
ABSTRACT
Introduction: Different pathological processes can deteriorate kidney function and cause ireversible degeneration of its structure; however, an optimal way to inhibit or slow down progression of renal damage is unforunately not available. In the light of promissing data concerning homeodomain-interacting protein kinase 2 (HIPK2) upregulation in damaged kidneys animal model, and increased levels of this protein in patients with various kidney diseases, the influence of rs7456421 and rs 2030712 single nucleotide polimorphisms of HIPK2 gene on chronic kidney disease incidence and progression was studied.
Material and methods: In 109 family ‘trios’, consisting of an affected child with CKD (48 females and 61 males, mean age 15.5 ±6.45 years) and both his/her parents, using Transmission Disequilibrium Test allele was used for the transfer of afore-mentioned SNPs from biological parents to their affected offspring.
Results: No statistical significance of allele transfer was found, which means that there were no associations between rs7456421 and rs 2030712 SNPs of HIPK2 gene and the incidence of renal dysfunction. Multiple stepwise regression showed a history of chronic glomerulonephritis (OR=17.3), chronic interstitial nephritis without urinary tract defect (OR=4.4), and CT genotype of rs 2030712 SNP (OR=2.6) as determinant of a more rapid progression of renal dysfunction, in contrast to the protective action of body mass index (OR=0.86).
Conclusions: On the basis of TDT results, the influence of rs7456421 and rs 2030712 SNPs of HIPK2 gene on prevalence of chronic kidney disease was not identified. Further studies are needed to ascertain the tight relationships of HIPK2 gene polymorphisms with CKD of different etiologies.
REFERENCES (26)
1.
Jin Y, Ratnam K, Chuang PY, Fan Y, Hong Y, Dai Y, et al. A systems approach identifies HIPK2 as a key regulator of kidney fibrosis. Nat Med. 2012; 18(4): 580-588.
2.
Kim YH, Choi CY, Lee SJ, Conti MA, Kim Y. Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors. J Biol Chem. 1998; 273(40): 25875-25879.
3.
Rinaldo C, Prodosmo A, Siepi F, Soddu S. HIPK2: a multitalented partner for transcription factors in DNA damage response and development. Biochem Cell Biol. 2007; 85(4): 411-418.
4.
Calzado MA, Renner F, Roscic A, Schmitz ML. HIPK2: a versatile switchboard regulating the transcription machinery and cell death. Cell Cycle. 2007; 6(2): 139-143.
5.
Bitomsky N, Hofmann TG. Apoptosis and autophagy: Regulation of apoptosis by DNA damage signalling – roles of p53, p73 and HIPK2. FEBS J. 2009; 276(21): 6074-6083.
6.
Iacovelli S, Ciuffini L, Lazzari C, Bracaglia G, Rinaldo C, Prodosmo A, et al. HIPK2 is involved in cell proliferation and its suppression promotes growth arrest independently of DNA damage. Cell Prolif. 2009; 42(3): 373-384.
7.
Isono K, Nemoto K, Li Y, Takada Y, Suzuki R, Katsuki M, et al. Overlapping roles for homeodomain-interacting protein kinases HIPK1 and HIPK2 in the mediation of cell growth in response to morphogenetic and genotoxic signals. Mol Cell Biol. 2006; 26(7): 2758- 2771.
8.
Pierantoni GM, Bulfone A, Pentimalli F, Fedele M, Iuliano R, Santoro M et al. The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues. Biochem Biophys Res Commun. 2002; 290(3): 942-947.
9.
Hofmann TG, Möller A, Sirma H, Zentgraf H, Taya Y, Dröge W, et. al Regulation of p53 activity by its interaction with homeodomaininteracting protein kinase-2. Nat Cell Biol. 2002; 4(1): 1-10.
10.
Sombroek D, Hofmann TG. How cells switch HIPK2 on and off. Cell Death Differ. 2009; 16(2): 187-194.
11.
de la Vega L, Fröbius K, Moreno R, Calzado MA, Geng H, Schmitz ML. Control of nuclear HIPK2 localization and function by a SUMO interaction motif. Biochim Biophys Acta. 2011; 1813(2): 283-297.
12.
Calzado MA, De La Vega L, Munoz E, Schmitz ML. From top to bottom: the two faces of HIPK2 for regulation of the hypoxic response. Cell Cycle. 2009; 8(11):1659-1664.
13.
Hailemariam K, Iwasaki K, Huang BW, Sakamoto K, Tsuji Y. Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress. J Cell Sci. 2010; 123(22): 3863-3871.
14.
Nardinocchi L, Puca R, D’Orazi G. HIF-1α antagonizes p53-mediated apoptosis by triggering HIPK2 degradation. Aging (Albany NY). 2011; 3(1): 33-43.
15.
Chalazonitis A, Tang AA, Shang Y, Pham TD, Hsieh I, Setlik W, et al. Homeodomain interacting protein kinase 2 regulates postnatal development of enteric dopaminergic neurons and glia via BMP signaling. J Neurosci. 2011; 31(39): 13746-137457.
16.
Zhang J, Pho V, Bonasera SJ, Holtzman J, Tang AT, Hellmuth J et al. Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nat Neurosci. 2007; 10(1): 77-86.
17.
Doxakis E, Huang EJ, Davies AM. Homeodomain-interacting protein kinase-2 regulates apoptosis in developing sensory and sympathetic neurons. Curr Biol. 2004; 14(19): 1761-1765.
18.
Aikawa Y, Nguyen LA, Isono K, Takakura N, Tagata Y, Schmitz ML et al. Roles of HIPK1 and HIPK2 in AML1- and p300-dependent transcription, hematopoiesis and blood vessel formation. EMBO J. 2006; 25(17): 3955-3965.
19.
Ohtsu N, Nobuhisa I, Mochita M, Taga T. Inhibitory effects of homeodomain-interacting protein kinase 2 on the aorta-gonadmesonephros hematopoiesis. Exp Cell Res. 2007; 313(1): 88-97.
20.
Puca R, Nardinocchi L, D’Orazi G. Regulation of vascular endothelial growth factor expression by homeodomain-interacting protein kinase-2. J Exp Clin Cancer Res. 2008; 27: 22.
21.
Nardinocchi L, Puca R, Givol D, D’Orazi G. HIPK2-a therapeutical target to be (re)activated for tumor suppression: role in p53 activation and HIF-1α inhibition. Cell Cycle. 2010; 9(7): 1270-1275.
22.
Puca R, Nardinocchi L, Givol D, D’Orazi G. Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells. Oncogene. 2010; 29(31): 4378-4387.
23.
Wei G, Ku S, Ma GK, Saito S, Tang AA, Zhang J et al. HIPK2 represses beta-catenin-mediated transcription, epidermal stem cell expansion, and skin tumorigenesis. Proc Natl Acad Sci U S A. 2007; 104(32): 13040-13045.
24.
Cao Z, Yoon JH, Nam SW, Lee JY, Park WS. Mutational analysis of the HIPK2 gene in keratoacanthoma and squamous cell carcinoma of the skin. APMIS. 2011; 119(6): 399-401.
25.
Krieghoff-Henning E, Hofmann TG. HIPK2 and cancer cell resistance to therapy. Future Oncol. 2008; 4(6): 751-754.
26.
Nardinocchi L, Puca R, Sacchi A, D’Orazi G. HIPK2 knock-down compromises tumor cell efficiency to repair damaged DNA. Biochem Biophys Res Commun. 2007; 361(1): 249-255.
Share
| eISSN: | 1898-2263 |
| ISSN: | 1232-1966 |
Improvement of visual identification of the journal - task financed under the agreement No. 618/P-DUN/2019 by the Minister of Science and Higher Education allocated to the activities of disseminating science.
Generation of the DOI (Digital Object Identifier) - task financed under the agreement No. 618/P-DUN/2019 by the Minister of Science and Higher
© 2006-2024 Journal hosting platform by Bentus
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
