Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지
DOI QR코드

DOI QR Code

Lack of association between the VEGFA gene polymorphisms and preterm birth in Korean women

  • Yue Shi (Department of Biological Sciences, College of Science & Technology, Dankook University) ;
  • Hyung Jun Kim (Department of Biological Sciences, College of Science & Technology, Dankook University) ;
  • Seong Yong Kim (Department of Biological Sciences, College of Science & Technology, Dankook University) ;
  • Ga Eun Kim (Department of Biological Sciences, College of Science & Technology, Dankook University) ;
  • Han Jun Jin (Department of Biological Sciences, College of Science & Technology, Dankook University)
  • Received : 2022.09.23
  • Accepted : 2023.06.24
  • Published : 2023.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Preterm birth (PTB), a pregnancy-related disease, is defined as a birth before 37 weeks of gestation. It is a major cause of maternal mortality and morbidity worldwide, and its incidence rate is steadily increasing. Various genetic factors can contribute to the etiology of PTB. Vascular endothelial growth factor A (VEGFA) gene is an important angiogenic gene and its polymorphisms have been reported to be associated with PTB development. Therefore, we conducted a case-control study to evaluate the association between VEGFA rs699947, rs2010963, and rs3025039 polymorphisms and PTB in Korean women. A total of 271 subjects (116 patients with PTB and 155 women at ≥38 weeks of gestation) were analyzed in this study. The genotyping of VEGFA gene polymorphisms was performed using polymerase chain reaction- restriction fragment length polymorphism. No significant association between the patients with PTB and the control groups was confirmed. In the combination analysis, we found a significant association between PTB and VEGFA rs699947 CC-rs2010963 GG-rs3025039 CC combination (odds ratio, 3.77; 95% confidence interval, 1.091 to 13.032; p = 0.031). The VEGFA rs699947, rs2010963, and rs3025039 polymorphisms might have no genetic association with the pathogenesis of PTB in Korean women. However, the combination analysis indicates the possibility that VEGFA acts in PTB pathophysiology. Therefore, larger sample sets and replication studies are required to further elucidate our findings.

Keywords

Acknowledgement

We are grateful to all volunteers for providing DNA samples. This work was supported by the National Research Foundation of Korea Grant funded by the Korea Government (NRF-2019R1D1A3A 03103804).

References

  1. Vogel JP, Chawanpaiboon S, Moller AB, Watananirun K, Bonet M, Lumbiganon P. The global epidemiology of preterm birth. Best Pract Res Clin Obstet Gynaecol 2018;52:3-12. https://doi.org/10.1016/j.bpobgyn.2018.04.003
  2. Walani SR. Global burden of preterm birth. Int J Gynaecol Obstet 2020;150:31-33. https://doi.org/10.1002/ijgo.13195
  3. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012;379:2162-2172. https://doi.org/10.1016/S0140-6736(12)60820-4
  4. Wagura P, Wasunna A, Laving A, Wamalwa D, Ng'ang'a P. Prevalence and factors associated with preterm birth at Kenyatta National Hospital. BMC Pregnancy Childbirth 2018;18:107.
  5. Kwon BN, Lee NR, Kim HJ, Kang YD, Kim JS, Park JW, et al. Folate metabolizing gene polymorphisms and genetic vulnerability to preterm birth in Korean women. Genes Genomics 2021;43: 937-945. https://doi.org/10.1007/s13258-021-01082-3
  6. Han YS, Ha EH, Park HS, Kim YJ, Lee SS. Relationships between pregnancy outcomes, biochemical markers and pre-pregnancy body mass index. Int J Obes (Lond) 2011;35:570-577. https://doi.org/10.1038/ijo.2010.162
  7. Bastek JA, Sammel MD, Pare E, Srinivas SK, Posencheg MA, Elovitz MA. Adverse neonatal outcomes: examining the risks between preterm, late preterm, and term infants. Am J Obstet Gynecol 2008;199:367.
  8. Lunde A, Melve KK, Gjessing HK, Skjaerven R, Irgens LM. Genetic and environmental influences on birth weight, birth length, head circumference, and gestational age by use of population-based parent-offspring data. Am J Epidemiol 2007;165:734-741. https://doi.org/10.1093/aje/kwk107
  9. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol 2008;111:35-41. https://doi.org/10.1097/01.AOG.0000297311.33046.73
  10. Svensson AC, Sandin S, Cnattingius S, Reilly M, Pawitan Y, Hultman CM, et al. Maternal effects for preterm birth: a genetic epidemiologic study of 630,000 families. Am J Epidemiol 2009; 170:1365-1372. https://doi.org/10.1093/aje/kwp328
  11. Todros T, Sciarrone A, Piccoli E, Guiot C, Kaufmann P, Kingdom J. Umbilical Doppler waveforms and placental villous angiogenesis in pregnancies complicated by fetal growth restriction. Obstet Gynecol 1999;93:499-503.
  12. Pang C, Lim CS, Brookes J, Tsui J, Hamilton G. Emerging importance of molecular pathogenesis of vascular malformations in clinical practice and classifications. Vasc Med 2020;25:364-377. https://doi.org/10.1177/1358863X20918941
  13. Andraweera PH, Dekker GA, Thompson SD, Nowak RC, Zhang JV, McCowan LM, et al. Association of vascular endothelial growth factor +936 C/T single-nucleotide polymorphism with pregnancies complicated by small-for-gestational-age babies. Arch Pediatr Adolesc Med 2011;165:1123-1130. https://doi.org/10.1001/archpediatrics.2011.796
  14. Crider KS, Whitehead N, Buus RM. Genetic variation associated with preterm birth: a HuGE review. Genet Med 2005;7:593-604. https://doi.org/10.1097/01.gim.0000187223.69947.db
  15. Guryanov I, Tennikova T, Urtti A. Peptide inhibitors of vascular endothelial growth factor A: current situation and perspectives. Pharmaceutics 2021;13:1337.
  16. Ruhrberg C. Growing and shaping the vascular tree: multiple roles for VEGF. Bioessays 2003;25:1052-1060. https://doi.org/10.1002/bies.10351
  17. Reynolds LP, Grazul-Bilska AT, Redmer DA. Angiogenesis in the corpus luteum. Endocrine 2000;12:1-9. https://doi.org/10.1385/ENDO:12:1:1
  18. Wada Y, Ozaki H, Abe N, Mori A, Sakamoto K, Nagamitsu T, et al. Role of vascular endothelial growth factor in maintenance of pregnancy in mice. Endocrinology 2013;154:900-910. https://doi.org/10.1210/en.2012-1967
  19. Holmes DI, Zachary I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol 2005;6:209.
  20. Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z. Association of VEGFA gene polymorphisms and VEGFA plasma levels with spontaneous preterm birth. Pharmacogenet Genomics 2015;25:199-204. https://doi.org/10.1097/FPC.0000000000000125
  21. Norwitz ER. A blood test to predict preterm birth: don't mess with maternal-fetal stress. J Clin Endocrinol Metab 2009;94: 1886-1889. https://doi.org/10.1210/jc.2009-0706
  22. Otrock ZK, Makarem JA, Shamseddine AI. Vascular endothelial growth factor family of ligands and receptors: review. Blood Cells Mol Dis 2007;38:258-268. https://doi.org/10.1016/j.bcmd.2006.12.003
  23. Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger E. A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vasc Res 2000;37:443-448. https://doi.org/10.1159/000054076
  24. Smith GC, Crossley JA, Aitken DA, Jenkins N, Lyall F, Cameron AD, et al. Circulating angiogenic factors in early pregnancy and the risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth. Obstet Gynecol 2007;109: 1316-1324. https://doi.org/10.1097/01.AOG.0000265804.09161.0d
  25. Almawi WY, Saldanha FL, Mahmood NA, Al-Zaman I, Sater MS, Mustafa FE. Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage. Hum Reprod 2013;28:2628-2635. https://doi.org/10.1093/humrep/det308
  26. Shahbazi M, Fryer AA, Pravica V, Brogan IJ, Ramsay HM, Hutchinson IV, et al. Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. J Am Soc Nephrol 2002;13:260-264. https://doi.org/10.1681/ASN.V131260
  27. Abhary S, Burdon KP, Gupta A, Lake S, Selva D, Petrovsky N, et al. Common sequence variation in the VEGFA gene predicts risk of diabetic retinopathy. Invest Ophthalmol Vis Sci 2009;50:5552-5558. https://doi.org/10.1167/iovs.09-3694
  28. Papazoglou D, Galazios G, Koukourakis MI, Kontomanolis EN, Maltezos E. Association of -634G/C and 936C/T polymorphisms of the vascular endothelial growth factor with spontaneous preterm delivery. Acta Obstet Gynecol Scand 2004;83: 461-465. https://doi.org/10.1111/j.0001-6349.2004.00403.x
  29. Zhao N, Wu W, Feng Y, Yang F, Han T, Guo M, et al. Polymorphisms in oxidative stress, metabolic detoxification, and immune function genes, maternal exposure to ambient air pollution, and risk of preterm birth in Taiyuan, China. Environ Res 2021;194: 110659.
  30. Diao LP, Yu XM, Gao YH, Li Y, Liu HS, Liu LH, et al. Association of VEGF genetic polymorphisms with the clinical characteristics of non-Hodgkin's lymphoma. J Cancer Res Clin Oncol 2009; 135:1473-1481. https://doi.org/10.1007/s00432-009-0650-0
  31. Han SW, Kim GW, Seo JS, Kim SJ, Sa KH, Park JY, et al. VEGF gene polymorphisms and susceptibility to rheumatoid arthritis. Rheumatology (Oxford) 2004;43:1173-1177. https://doi.org/10.1093/rheumatology/keh281
  32. Kim SH, Choi YM, Choung SH, Jun JK, Kim JG, Moon SY. Vascular endothelial growth factor gene +405 C/G polymorphism is associated with susceptibility to advanced stage endometriosis. Hum Reprod 2005;20:2904-2908. https://doi.org/10.1093/humrep/dei146
  33. Armstrong RA. When to use the Bonferroni correction. Ophthalmic Physiol Opt 2014;34:502-508. https://doi.org/10.1111/opo.12131
  34. Mowa CN, Jesmin S, Sakuma I, Usip S, Togashi H, Yoshioka M, et al. Characterization of vascular endothelial growth factor (VEGF) in the uterine cervix over pregnancy: effects of denervation and implications for cervical ripening. J Histochem Cytochem 2004; 52:1665-1674. https://doi.org/10.1369/jhc.4A6455.2004
  35. Monangi NK, Brockway HM, House M, Zhang G, Muglia LJ. The genetics of preterm birth: progress and promise. Semin Perinatol 2015;39:574-583. https://doi.org/10.1053/j.semperi.2015.09.005
  36. Al-Khateeb GM, Mustafa FE, Sater MS, Almawi WY. Effect of the functional VEGFA-583C/T variant on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage. Fertil Steril 2011;95:2471-2473. https://doi.org/10.1016/j.fertnstert.2011.03.010
  37. Lin TH, Wang CL, Su HM, Hsu PC, Juo SH, Voon WC, et al. Functional vascular endothelial growth factor gene polymorphisms and diabetes: effect on coronary collaterals in patients with significant coronary artery disease. Clin Chim Acta 2010; 411:1688-1693. https://doi.org/10.1016/j.cca.2010.07.002
  38. Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 2000;12:1232-1235. https://doi.org/10.1006/cyto.2000.0692
  39. Crump C, Sundquist J, Sundquist K. Association of preterm birth with lipid disorders in early adulthood: a Swedish cohort study. PLoS Med 2019;16:e1002947.
  40. Papageorgiou L, Andreou A, Zervou M, Vlachakis D, Goulielmos GN, Eliopoulos E. A global population genomic analysis shows novel insights into the genetic characteristics of endometriosis. World Acad Sci J 2023;5:12.
  41. Cardon LR, Bell JI. Association study designs for complex diseases. Nat Rev Genet 2001;2:91-99. https://doi.org/10.1038/35052543
  42. Shang CY, Gau SS, Liu CM, Hwu HG. Association between the dopamine transporter gene and the inattentive subtype of attention deficit hyperactivity disorder in Taiwan. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:421-428. https://doi.org/10.1016/j.pnpbp.2010.08.016
  43. Correa-Noronha SA, Noronha SM, Alecrim C, Mesquita Ade C, Brito GS, Junqueira MG, et al. Association of angiotensin-converting enzyme I gene I/D polymorphism with endometrial but not with ovarian cancer. Gynecol Endocrinol 2012;28:889-891. https://doi.org/10.3109/09513590.2012.683060
  44. Hattersley AT, McCarthy MI. What makes a good genetic association study? Lancet 2005;366:1315-1323. https://doi.org/10.1016/S0140-6736(05)67531-9
  45. Popejoy AB, Fullerton SM. Genomics is failing on diversity. Nature 2016;538:161-164. https://doi.org/10.1038/538161a