Abstract
Purpose
The aim of this study was to investigate whether polymorphisms in the tissue inhibitor of metalloproteinase 3 gene (TIMP3) are associated with the risk of preeclampsia (PE) in Han Chinese women.
Methods
Nine single TIMP3 tag-single nucleotide polymorphisms were selected by Haploview and genotyped using the Sequenom method in 181 preeclamptic and 203 healthy pregnant women from eastern China.
Results
The allele frequencies of the tag-single nucleotide polymorphisms were not significantly different between groups (P > 0.05). However, the genotype distribution of rs135025 was shown to differ between the multigravidity PE subgroup (>3) and controls under additive (P = 0.018) and recessive models (P = 0.008), while the genotype distribution of rs80272 differed significantly between the severe PE subgroup and controls under additive (P = 0.014) and dominant models (P = 0.041). Moreover, the H2 haplotype (A-C-G-T-A-A-G-C-G) was found to be associated with the risk of PE (P = 0.035).
Conclusions
Genotypes of rs135025 and rs80272 in TIMP3 may therefore influence susceptibility to PE, and pregnant women carrying the H2 haplotype might be more prone to developing PE.
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References
Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308:1592–4.
Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006;367:1066–74.
Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365:785–99.
AbouZahr C. Global burden of maternal death and disability. Br Med Bull. 2003;67:1–11.
Anonymous. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol. 2002; 99:159-67.
Wan JP, Zhao H, Li T, Li CZ, Wang XT, Chen ZJ. The common variant rs11646213 is associated with preeclampsia in Han Chinese women. PLoS One. 2013;8, e71202.
Chen X, Gan T, Liao Z, Chen S, Xiao J. Foxp3 (-/ATT) polymorphism contributes to the susceptibility of preeclampsia. PLoS One. 2013;8, e59696.
Li J, Liu M, Zong J, Tan P, Wang J, Wang X, et al. Genetic variations in IL1A and IL1RN are associated with the risk of preeclampsia in Chinese Han population. Sci Rep. 2014;4:5250.
Cruz-Munoz W, Sanchez OH, Di Grappa M, English JL, Hill RP, Khokha R. Enhanced metastatic dissemination to multiple organs by melanoma and lymphoma cells in timp-3-/- mice. Oncogene. 2006;25:6489–96.
Qi JH, Ebrahem Q, Moore N, Murphy G, Claesson-Welsh L, Bond M, et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med. 2003;9:407–15.
Baker AH, George SJ, Zaltsman AB, Murphy G, Newby AC. Inhibition of invasion and induction of apoptotic cell death of cancer cell lines by overexpression of TIMP-3. Br J Cancer. 1999;79:1347–55.
Peterson NB, Beeghly-Fadiel A, Gao YT, Long J, Cai Q, Shu XO, et al. Polymorphisms in tissue inhibitors of metalloproteinases-2 and -3 and breast cancer susceptibility and survival. Int J Cancer. 2009;125:844–50.
BenEzra D. Inhibition of angiogenesis by tissue inhibitor of metalloproteinase-3. Invest Ophthalmol Vis Sci. 1997;38:2433–4.
Boon K, Osorio EC, Greenhut SF, Schaefer CF, Shoemaker J, Polyak K, et al. An anatomy of normal and malignant gene expression. Proc Natl Acad Sci U S A. 2002;99:11287–92.
Xiang Y, Zhang X, Li Q, Xu J, Zhou X, Wang T, et al. Promoter hypomethylation of TIMP3 is associated with pre-eclampsia in a Chinese population. Mol Hum Reprod. 2013;19:153–9.
Yuen RK, Penaherrera MS, von Dadelszen P, McFadden DE, Robinson WP. DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia. Eur J Hum Genet. 2010;18:1006–12.
Pereza N, Volk M, Zrakic N, Kapovic M, Peterlin B, Ostojic S. Genetic variation in tissue inhibitors of metalloproteinases as a risk factor for idiopathic recurrent spontaneous abortion. Fertil Steril. 2013;99:1923–9.
Ewens KG, George RA, Sharma K, Ziyadeh FN, Spielman RS. Assessment of 115 candidate genes for diabetic nephropathy by transmission/disequilibrium test. Diabetes. 2005;54:3305–18.
Huang R, Deng L, Shen A, Liu J, Ren H, Xu DL. Associations of MMP1, 3, 9 and TIMP3 genes polymorphism with isolated systolic hypertension in Chinese Han population. Int J Med Sci. 2013;10:840–7.
Fauser S, Smailhodzic D, Caramoy A, van de Ven JP, Kirchhof B, Hoyng CB, et al. Evaluation of serum lipid concentrations and genetic variants at high-density lipoprotein metabolism loci and TIMP3 in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52:5525–8.
NHBPEPWG. Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000;183:S1–22.
Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.
International-HapMap-Consortium. The international HapMap project. Nature. 2003;426:789–96.
Zhu C, Yu ZB, Chen XH, Ji CB, Qian LM, Han SP. DNA hypermethylation of the NOX5 gene in fetal ventricular septal defect. Exp Ther Med. 2011;2:1011–5.
Tian W, Zhao L, Wang J, Suo P, Cheng L, Cheng Z, et al. Association analysis between HOXD9 genes and the development of developmental dysplasia of the hip in Chinese female Han population. BMC Musculoskelet Disord. 2012;13:59.
Li Z, Zhang Z, He Z, Tang W, Li T, Zeng Z, et al. A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http://analysis.bio-x.cn). Cell Res. 2009;19:519–23.
Shi YY, He L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005;15:97–8.
Gurdol F, Yurdum LM, Ozturk U, Isbilen E, Cakmakoglu B. Association of the CC chemokine receptor 5 (CCR5) polymorphisms with preeclampsia in Turkish women. Arch Gynecol Obstet. 2012;286:51–4.
Sowmya S, Ramaiah A, Sunitha T, Nallari P, Jyothy A, Venkateshwari A. Role of IL-10 -819(t/c) promoter polymorphism in preeclampsia. Inflammation. 2014;37:1022–7.
Rahimi Z, Aghaei A, Vaisi-Raygani A. AT2R -1332 G:A polymorphism and its interaction with AT1R 1166 A:C, ACE I/D and MMP-9 -1562 C:T polymorphisms: risk factors for susceptibility to preeclampsia. Gene. 2014;538:176–81.
Seremak-Mrozikiewicz A, Drews K, Barlik M, Sieroszewski P, Grzeskowiak E, Mrozikiewicz P. The significance of -786T > C polymorphism of endothelial NO synthase (eNOS) gene in severe preeclampsia. J Matern Fetal Neonatal Med. 2011;24:432–6.
Loffek S, Schilling O, Franzke CW. Series “matrix metalloproteinases in lung health and disease”: biological role of matrix metalloproteinases: a critical balance. Eur Respir J. 2011;38:191–208.
Lee MH, Atkinson S, Murphy G. Identification of the extracellular matrix (ECM) binding motifs of tissue inhibitor of metalloproteinases (TIMP)-3 and effective transfer to TIMP-1. J Biol Chem. 2007;282:6887–98.
Yu WH, Yu S, Meng Q, Brew K, Woessner Jr JF. TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. J Biol Chem. 2000;275:31226–32.
Leco KJ, Khokha R, Pavloff N, Hawkes SP, Edwards DR. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix-associated protein with a distinctive pattern of expression in mouse cells and tissues. J Biol Chem. 1994;269:9352–60.
Karthikeyan VJ, Lane DA, Beevers DG, Lip GY, Blann AD. Matrix metalloproteinases and their tissue inhibitors in hypertension-related pregnancy complications. J Hum Hypertens. 2013;27:72–8.
Spinale FG. Matrix metalloproteinases: regulation and dysregulation in the failing heart. Circ Res. 2002;90:520–30.
Knox JB, Sukhova GK, Whittemore AD, Libby P. Evidence for altered balance between matrix metalloproteinases and their inhibitors in human aortic diseases. Circulation. 1997;95:205–12.
Fan D, Takawale A, Basu R, Patel V, Lee J, Kandalam V, et al. Differential role of TIMP2 and TIMP3 in cardiac hypertrophy, fibrosis, and diastolic dysfunction. Cardiovasc Res. 2014;103:268–80.
Armstrong C, Abilleira S, Sitzer M, Markus HS, Bevan S. Polymorphisms in MMP family and TIMP genes and carotid artery intima-media thickness. Stroke. 2007;38:2895–9.
Smookler DS, Mohammed FF, Kassiri Z, Duncan GS, Mak TW, Khokha R. Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation. J Immunol. 2006;176:721–5.
Lee MH, Rapti M, Murphy G. Total conversion of tissue inhibitor of metalloproteinase (TIMP) for specific metalloproteinase targeting: fine-tuning TIMP-4 for optimal inhibition of tumor necrosis factor-{alpha}-converting enzyme. J Biol Chem. 2005;280:15967–75.
Wang Y, Wang Q, Guo C, Wang S, Wang X, An L, et al. Association between CRP gene polymorphisms and the risk of preeclampsia in Han Chinese women. Genet Test Mol Biomark. 2014;18:775–80.
Wang X, Jiang F, Liang Y, Xu L, Li H, Liu Y, et al. Interleukin-1beta-31C/T and -511T/C polymorphisms were associated with preeclampsia in Chinese Han population. PLoS One. 2014;9, e106919.
Kobayashi N, Hanaoka M, Droma Y, Ito M, Katsuyama Y, Kubo K, et al. Polymorphisms of the tissue inhibitor of metalloproteinase 3 gene are associated with resistance to high-altitude pulmonary edema (HAPE) in a Japanese population: a case control study using polymorphic microsatellite markers. PLoS One. 2013;8, e71993.
Anacker J, Segerer SE, Hagemann C, Feix S, Kapp M, Bausch R, et al. Human decidua and invasive trophoblasts are rich sources of nearly all human matrix metalloproteinases. Mol Hum Reprod. 2011;17:637–52.
Sheppard SJ, Khalil RA. Risk factors and mediators of the vascular dysfunction associated with hypertension in pregnancy. Cardiovasc Hematol Disord Drug Targets. 2010;10:33–52.
Montagnana M, Lippi G, Albiero A, Scevarolli S, Salvagno GL, Franchi M, et al. Evaluation of metalloproteinases 2 and 9 and their inhibitors in physiologic and pre-eclamptic pregnancy. J Clin Lab Anal. 2009;23:88–92.
Tayebjee MH, Karalis I, Nadar SK, Beevers DG, MacFadyen RJ, Lip GY. Circulating matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 and -2 levels in gestational hypertension. Am J Hypertens. 2005;18:325–9.
Acknowledgments
We thank Professor Hui Li from Shengjing Hospital of China Medical University for providing samples. We especially thank all of the participants for their contributions to the research. This study was supported by the National International Scientific and Technological Cooperation Programme 2012DFB30130.
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The authors declare that they have no conflict of interest.
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Capsule TIMP3 rs135025 and rs80272 polymorphisms may influence susceptibility to PE in Han Chinesewomen.
Changlong Guo and Xiaofang Cao These two authors equally contributed to this work.
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Guo, C., Cao, X., Wang, Q. et al. Contribution of TIMP3 polymorphisms to the development of preeclampsia in Han Chinese women. J Assist Reprod Genet 32, 1525–1530 (2015). https://doi.org/10.1007/s10815-015-0529-8
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DOI: https://doi.org/10.1007/s10815-015-0529-8