Volume 13, Issue 12 (12-2015)                   IJRM 2015, 13(12): 755-764 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
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. IJRM 2015; 13 (12) :755-764
URL: http://ijrm.ir/article-1-614-en.html
Association of kinase insert domain-containing receptor (KDR) gene polymorphism/ haplotypes with recurrent spontaneous abortion and genetic structure
Shiva Shahsavari1 , Zahra Noormohammadi * 2, Shohreh Zare Karizi3
1- Department of Biology, School of Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
2- Department of Biology, School of Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran , marjannm@yahoo.com
3- Department of Biology, Pishva Branch, Islamic Azad University, Varamin, Iran
Abstract:   (2878 Views)
Background: Recurrent spontaneous abortion is one of the diseases that can lead to physical, psychological, and, economical problems for both individuals and society. Recently a few numbers of genetic polymorphisms in kinase insert domain-containing receptor (KDR) gene are examined that can endanger the life of the fetus in pregnant women. Objective: The risk of KDR gene polymorphisms was investigated in Iranian women with idiopathic recurrent spontaneous abortion (RSA). Materials and Methods: A case controlled study was performed. One hundred idiopathic recurrent spontaneous abortion patients with at least two consecutive pregnancy losses before 20 weeks of gestational age with normal karyotypes were included in the study. Also, 100 healthy women with at least one natural pregnancy were studied as control group. Two functional SNPs located in KDR gene; rs1870377 (Q472H), and rs2305948 (V297I) as well as one tag SNP in the intron region (rs6838752) were genotyped by using PCR based restriction fragment length polymorphism (PCR-RFLP) technique. Haplotype frequency was determined for these three SNPs’ genotypes. Analysis of genetic STRUCTURE and K means clustering were performed to study genetic variation. Results: Functional SNP (rs1870377) was highly linked to tag SNP (rs6838752) (D´ value=0. 214; χ2 = 16.44, p<0. 001). K means clustering showed that k = 8 as the best fit for the optimal number of genetic subgroups in our studied materials. This result was in agreement with Neighbor Joining cluster analysis. Conclusion: In our study, the allele and genotype frequencies were not associated with RSA between patient and control individuals. Inconsistent results in different populations with different allele frequencies among RSA patients and controls may be due to ethnic variation and used sample size.  
Keywords: Abortion, Genetic structures, Polymorphism, Restriction fragment length polymorphism, VEGF receptor 2
Full-Text [PDF 770 kb]   (961 Downloads) |   |   Full-Text (HTML)  (372 Views)  
Type of Study: Original Article |
References
1. Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss. Fertil Steril 2008; 90: S60. [DOI:10.1016/j.fertnstert.2008.08.065]
2. Sondheimer S: Abortion. Encycl Reprod 1999; 1: 1-6.
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]
4. Stirrat GM. Recurrent miscarriage. Lancet 1990; 336: 673–675. [DOI:10.1016/0140-6736(90)92159-F]
5. 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]
6. 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]
7. Lee HH, Hong SH, Shin SJ, Ko JJ, Oh D, Kim NK. Association study of vascular endothelial growth factor polymorphisms with the risk of recurrent spontaneous abortion. Fertil Steril 2010; 93: 1244–1247. [DOI:10.1016/j.fertnstert.2008.11.017]
8. 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]
9. 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]
10. An SJ, Chen ZH, Lin QX, Su J, Chen HJ, Lin JY, et al. The- 271 G>A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer. BMC Cancer 2009; 9: 144. [DOI:10.1186/1471-2407-9-144]
11. 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]
12. Sole´X, Guino´ E, Valls J, Iniesta R, Moreno V. SNPstats: a web tool for the analysis of association studies. Bioinformatics 2006; 22: 1928–1929. [DOI:10.1093/bioinformatics/btl268]
13. Weising K, Nybom H, Wolf K, Kahl G. DNA Finger Printing in Plants. 2nd Ed. New York; CRC Press, Taylor and Francis; 2005. [DOI:10.1201/9781420040043]
14. Freeland JR, Kirk H, Peterson, S.D. Molecular Ecology . 2nd Ed. UK; Wiley-Blackwell; 2011. [DOI:10.1002/9780470979365]
15. Peakall R, Smouse PE. GENALEX 6: genetic analysis in excel. population genetic software for teaching and research. Mol Ecol Notes 2006; 6: 288- 295. [DOI:10.1111/j.1471-8286.2005.01155.x]
16. Earl, DA, von Holdt BM. STRUCTURE HARVESTER: a website and program for visualizing STRUCTURE output and implementing the Evanno method. Conserv Genet Resour 2012; 4: 359-361. [DOI:10.1007/s12686-011-9548-7]
17. Evanno G, Regnaut S, Goudet J. Detecting the number of clusters of individuals using the software STRUCTURE: a simulation study. Mol Ecol 2005; 14: 2611-2620. [DOI:10.1111/j.1365-294X.2005.02553.x]
18. Calinski R, Harabasz J. A dendrite method for cluster analysis. Commun Stat 1974; 3: 1-27.
19. Schwarz G. Estimating the dimension of a model. Ann Stat 1978; 6: 461-464. [DOI:10.1214/aos/1176344136]
20. Meirmans PG, Van Tienderen PH. GENOTYPE and GENODIVE: two programs for the analysis of genetic diversity of asexual organisms. Mol Ecol Notes 2004; 4: 792-794. [DOI:10.1111/j.1471-8286.2004.00770.x]
21. Greene JM, Dunaway CW, Bowers SD, Rude BJ, Feugang JM, Ryan PL. In vivo monitoring of fetoplacental Vegfr2 gene activity in a murine pregnancy model using a Vegfr2-luc reporter gene and bioluminescent imaging. Reprod Biol Endocrinol 2011; 9: 51. [DOI:10.1186/1477-7827-9-51]
22. Bogic LV, Brace RA, Cheung CY. Developmental expression of vascular endothelial growth factor (VEGF) receptors and VEGF binding in ovine placenta and fetal membranes. Placenta 2001; 22: 265–275. [DOI:10.1053/plac.2001.0627]
23. Sugino N, Kashida S, Karube-Harada A, Takiguchi S, Kato H. Expression of vascular endothelial growth factor (VEGF) and its receptors in human endometrium throughout the menstrual cycle and in early pregnancy. Reproduction 2002; 123: 379–387. [DOI:10.1530/rep.0.1230379]
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