Volume 17, Issue 7 (July 2019 2019)                   IJRM 2019, 17(7): 473-480 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Keshavarz L, Yavarian M. The association of Q472H variant in the KDR gene with recurrent pregnancy loss in Southern Iran: A case-control study. IJRM 2019; 17 (7) :473-480
URL: http://ijrm.ir/article-1-1579-en.html
The association of Q472H variant in the KDR gene with recurrent pregnancy loss in Southern Iran: A case-control study
Leila Keshavarz1 , Majid Yavarian * 2
1- Department of Biology, Islamic Azad University, Arsanjan Branch, Arsanjan, Iran.
2- Shiraz Nephron-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran , yavarian@sums.ac.ir
Abstract:   (2173 Views)
Background: Recurrent spontaneous abortion (RSA) often remains unclear and can be burden for the patient and time consuming for clinician. RSA may initiates from a genetic or non-genetic factors. It is well known that the quality of placental circulation is critical for implantation and embryo development. Because of angiogenic effects of VEGF–KDR pathway on placenta, the genes involved in this pathway (the KDR or VEGFR genes) are thought to be linked with RSA.
Objective: The aim of this study was to investigate the relationship between Gln472His (A/T) polymorphism of the KDR gene with RSAs in southern Iran.
Materials and Methods: In this case-control study, 50 aborted embryonic tissue obtained from fetuses and 50 umbilical cord blood of newborn babies were studied.
Fetal sample from mothers with history of at least two consecutive miscarriages and controls from mothers who had at least one full-term infants born were taken. Genomic DNA was extracted by using PureLink genomic DNA kit (Life Technologies, CA). The Rotor-Gene Q real-Time PCR machine and High-resolution melting curve analysis (HRM) technique were used for genotyping.
Results: Based on the AA genotype as reference, it is shown that the T allele (OR =2.447, 95% CI = 1.095–5.468, p = 0.029) as well as AT heterozygote genotype was significantly associated with an increased risk of miscarriage (OR = 2.824, 95% CI = 1.210-6.673, p = 0.016).
Conclusion: A positive correlation between Q472H polymorphism of the KDR gene and RSA may be the cause in southern Iran.
Keywords: Abortion, VEGFR 2, Polymorphism
Full-Text [PDF 416 kb]   (755 Downloads) |   |   Full-Text (HTML)  (372 Views)  
Type of Study: Original Article |
References
1. Carrington B, Sacks G, Regan L. Recurrent miscarriage: pathophysiology and outcome. Curr Opin Obstet Gynecol 2005; 17: 591-597. [DOI:10.1097/01.gco.0000194112.86051.26] [PMID]
2. Stirrat GM. Recurrent miscarriage. Lancet 1990; 336: 673-675. [DOI:10.1016/0140-6736(90)92159-F]
3. Clifford K, Rai R, Watson H, Regan L. An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases. Hum Reprod 1994; 9: 1328-1332. [DOI:10.1093/oxfordjournals.humrep.a138703] [PMID]
4. Stirrat GM. Recurrent miscarriage. II: Clinical associations, causes, and management. Lancet 1990; 336: 728-733. [DOI:10.1016/0140-6736(90)92215-4]
5. Simpson JL, Golbus MS. Genetics in obstetrics and gynecology. 2nd Ed. Philadelphia: W.B. Saunders Inc; 1992: 181-200.
6. Rai R, Regan L. Recurrent miscarriage. Lancet 2006; 368: 601-611. [DOI:10.1016/S0140-6736(06)69204-0]
7. Stephenson MD. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril 1996; 66: 24-29. [DOI:10.1016/S0015-0282(16)58382-4]
8. Benjamin LE, Keshet E. Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc Natl Acad Sci USA 1997; 94: 8761-8766. [DOI:10.1073/pnas.94.16.8761] [PMID] [PMCID]
9. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9: 669-676. [DOI:10.1038/nm0603-669] [PMID]
10. Jelkmann W. Pitfalls in the measurement of circulating vascular endothelial growth factor. Clin Chem 2001; 47: 617-623.
11. Su MT, Lin SH, Lee IW, Chen YC, Kuo PL. Association of polymorphisms/haplotypes of the genes encoding vascular endothelial growth factor and its KDR receptor with recurrent pregnancy loss. Hum Reprod 2011; 26: 758-764. [DOI:10.1093/humrep/deq401] [PMID]
12. Ferrara N, Davis-Smith T. The biology of vascular endothelial growth factor. Endocr Rev 1997; 18: 4-25. [DOI:10.1210/edrv.18.1.0287] [PMID]
13. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23: 1011-1027. [DOI:10.1200/JCO.2005.06.081] [PMID]
14. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004; 25: 581-611. [DOI:10.1210/er.2003-0027] [PMID]
15. Reynolds LP, Redmer DA. Angiogenesis in the placenta. Biol Reprod 2001; 64: 1033-1040. [DOI:10.1095/biolreprod64.4.1033] [PMID]
16. Demir R, Kayisli UA, Seval Y, Celik-Ozenci C, Korgun ET, Demir-Weusten AY, et al. Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: differences between placental vasculogenesis and angiogenesis. Placenta 2004; 25: 560-572. [DOI:10.1016/j.placenta.2003.11.011] [PMID]
17. Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res 2006; 312: 549-560. [DOI:10.1016/j.yexcr.2005.11.012] [PMID]
18. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995; 376: 62-66. [DOI:10.1038/376062a0] [PMID]
19. Park YS, Jeon YJ, Kim HS, Chae KY, Oh SH, Han IB, et al. The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization. PLoS One 2012; 7: e47158. [DOI:10.1371/journal.pone.0047158] [PMID] [PMCID]
20. Rah H, Jeon YJ, Lee BE, Choi DH, Yoon TK, Lee WS, et al. Association of kinase insert domain-containing receptor (KDR) gene polymorphisms with idiopathic recurrent spontaneous abortion in korean women. Fertil Steril 2013; 99: 753-760. [DOI:10.1016/j.fertnstert.2012.10.038] [PMID]
21. Wang Y, Zheng Y, Zhang W, Yu H, Lou K, Zhang Y, et al. Polymorphisms of KDR gene are associated with coronary heart disease. J Am Coll Cardiol 2007; 50: 760-767. [DOI:10.1016/j.jacc.2007.04.074] [PMID]
22. Honarvar N, Sheikhha MH, Farashahi Yazd E, Pashaiefar H, Mohtaram S, Sazegari A, et al. KDR gene polymorphisms and idiopathic recurrent spontaneous abortion. J Matern Fetal Neonatal Med 2016; 29: 3737-3740. [DOI:10.3109/14767058.2016.1142966] [PMID]
23. Shahsavari S, Noormohammadi Z, Zare Karizi S. Association of kinase insert domain-containing receptor (KDR) gene polymorphism/ haplotypes with recurrent spontaneous abortion and genetic structure. Int J Reprod Biomed 2015; 13: 755-764. [DOI:10.29252/ijrm.13.12.755]
24. Giudice LC. Potential biochemical markers of uterine receptivity. Hum Reprod 1999; 14 (Suppl.): 3-16. [DOI:10.1093/humrep/14.suppl_2.3] [PMID]
25. Sharkey A. Cytokines and implantation. Rev Reprod 1998; 3: 52-61. [DOI:10.1530/ror.0.0030052] [PMID]
26. Kimber SJ, Spanswick C. Blastocyst implantation: the adhesion cascade. Semin Cell Dev Biol 2000; 11: 77-92. [DOI:10.1006/scdb.2000.0154] [PMID]
27. Tammela T, Enholm B, Alitalo K, Paavonen K. The biology of vascular endothelial growth factors. Cardiovasc Res 2005; 65: 550-563. [DOI:10.1016/j.cardiores.2004.12.002] [PMID]
28. Habara T, Nakatsuka M, Konishi H, Asagiri K, Noguchi S, Kudo T. Elevated blood flow resistance in uterine arteries of women with unexplained recurrent pregnancy loss. Hum Reprod 2002; 17: 190-194. [DOI:10.1093/humrep/17.1.190] [PMID]
29. Goswamy RK, Williams G, Steptoe PC. Decreased uterine perfusion--a cause of infertility. Hum Reprod 1988; 3: 955-959. [DOI:10.1093/oxfordjournals.humrep.a136825] [PMID]
30. Zygmunt M, Herr F, Munstedt K, Lang U, Liang OD. Angiogenesis and vasculogenesis in pregnancy. Eur J Obstet Gynecol Reprod Biol 2003; 110 (Suppl.): 8-10. [DOI:10.1016/S0301-2115(03)00168-4]
31. Daher S, Mattar R, Gueuvoghlanian-Silva BY, Torloni MR. Genetic polymorphisms and recurrent spontaneous abortions: an overview of current knowledge. Am J Reprod Immunol 2012; 67: 341-347. [DOI:10.1111/j.1600-0897.2012.01123.x] [PMID]
32. Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L. VEGF-receptor signal transduction. Trends Biochem Sci 2003; 28: 488-494. [DOI:10.1016/S0968-0004(03)00193-2]
33. Kariyazono H, Ohno T, Khajoee V, Ihara K, Kusuhara K, Kinukawa N, et al. Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene polymorphisms with coronary artery lesions of Kawasaki disease. Pediatr Res 2004; 56: 953-959. [DOI:10.1203/01.PDR.0000145280.26284.B9] [PMID]
34. Galan A, Ferlin A, Caretti L, Buson G, Sato G, Frigo AC, et al. Association of age-related macular degeneration with polymorphisms in vascular endothelial growth factor and its receptor. Ophthalmology 2010; 117: 1769-1774. [DOI:10.1016/j.ophtha.2010.01.030] [PMID]
35. Hiratsuka S, Kataoka Y, Nakao K, Nakamura K, Morikawa S, Tanaka S, et al. Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF-receptor positive cells to the anterior portion of early embryos. Mol Cell Biol 2005; 25: 355-363. [DOI:10.1128/MCB.25.1.355-363.2005] [PMID] [PMCID]
36. Glubb DM, Cerri E, Giese E, Zhang W, Mirza O, Thompson EE, et al. Novel functional germline variants in the vascular endothelial growth factor receptor 2 gene and their effect on gene expression and microvessel density in lung cancer. Clin Cancer Res 2011; 17: 5257-5267. [DOI:10.1158/1078-0432.CCR-11-0379] [PMID] [PMCID]
37. Su MT, Lin SH, Chen YC. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod Update 2011; 17: 803-812. [DOI:10.1093/humupd/dmr027] [PMID]
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb