Angiogenesis and oxidative stress-related gene variants in recurrent pregnancy loss
Marcela Felix Fortis A , Lucas Rosa Fraga A B C G , Juliano André Boquett A B , Thayne Woycinck Kowalski A , Caroline Gross Dutra A , Rozana Oliveira Gonçalves D , Fernanda Sales Luiz Vianna A B C E , Lavinia Schüler-Faccini A B C and Maria Teresa Vieira Sanseverino A B C F G
+ Author Affiliations
- Author Affiliations
A Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, 91501-970, Brazil.
B National Institute of Population Medical Genetics (INaGeMP), Porto Alegre, 91501-970, Brazil.
C National System for Information on Teratogenic Agents (SIAT), Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035- 903, Brazil.
D Obstetrics, Gynaecology and Human Reproduction Department, Federal University of Bahia, Salvador, 40110-100, Brazil.
E Genomic Medicine Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035- 903, Brazil.
F School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, 90610-000, Brazil.
G Corresponding authors. Emails: msanseverino@hcpa.edu.br; lrf.fraga@gmail.com
Reproduction, Fertility and Development 30(3) 498-506 https://doi.org/10.1071/RD17117
Submitted: 24 March 2017 Accepted: 23 July 2017 Published: 22 August 2017
Abstract
Recurrent pregnancy loss (RPL) affects ~3–5% of couples attempting to conceive and in around 50% of cases the aetiology remains unknown. Adequate vascularisation and placental circulation are indispensable for the development of a normal pregnancy. Prostaglandin-endoperoxide synthase 2 (PTGS2), vascular endothelial growth factor (VEGF) and the nitric oxide (NO) systems play important roles in reproductive physiology, participating in several steps including implantation and apoptosis of trophoblast cells. In this study we evaluated genetic polymorphisms in the inducible nitric oxide synthase (NOS2), PTGS2 and VEGFA genes as susceptibility factors for RPL. A case-control study was conducted in 149 women having two or more miscarriages and 208 controls. Allele and genotype distributions of the polymorphisms studied in the two groups were not statistically different. However, the dominant model showed that the presence of variant T (TT/GT) of rs2779249 (−1290G > T) of NOS2 was significantly associated with RPL (OR = 1.58, CI 95% = 1.03–2.44; P = 0.037). The increased risk remained significant when adjusted for number of pregnancies, alcohol consumption and ethnicity (OR = 1.92, CI95% = 1.18–3.11; P = 0.008). These results suggest that the variant genotypes of the functional polymorphism rs2779249 in the NOS2 promoter are a potential risk for RPL, possibly due to oxidative stress mechanisms.
Additional keywords: genetics, infertility, miscarriage, repeated miscarriage.
References
Agarwal, A., Aponte-Mellado, A., Premkumar, B. J., Shaman, A., and Gupta, S. (2012). The effects of oxidative stress on female reproduction: a review. Reprod. Biol. Endocrinol. 10, 49.| The effects of oxidative stress on female reproduction: a review.Crossref | GoogleScholarGoogle Scholar |
Aggarwal, S., Parveen, F., Faridi, R. M., Phadke, S., Borkar, M., and Agrawal, S. (2011). Vascular endothelial growth factor gene polymorphisms in North Indian patients with recurrent miscarriages. Reprod. Biomed. Online 22, 59–64.
| Vascular endothelial growth factor gene polymorphisms in North Indian patients with recurrent miscarriages.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXisVCisrs%3D&md5=7ca0e503f8d859758bf92118575dc1c7CAS |
Al-Khateeb, G. M., Mustafa, F. E., Sater, M. S., and Almawi, W. Y. (2011). Effect of the functional VEGFA-583C/T variant on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage. Fertil. Steril. 95, 2471–2473.
| Effect of the functional VEGFA-583C/T variant on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXot1aksbw%3D&md5=5f07e5c70a6510ad58fbf9195d361afbCAS |
Almawi, W. Y., Saldanha, F. L., Mahmood, N. A., Al-Zaman, I., Sater, M. S., and Mustafa, F. E. (2013). Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage. Hum. Reprod. 28, 2628–2635.
| Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsFegt7jJ&md5=0a5c0fd4c7678bbeaec04789ca385a55CAS |
Amaral, L. M., Palei, A. C., Sandrim, V. C., Luizon, M. R., Cavalli, R. C., Duarte, G., and Tanus-Santos, J. E. (2012). Maternal iNOS genetic polymorphisms and hypertensive disorders of pregnancy. J. Hum. Hypertens. 26, 547–552.
| Maternal iNOS genetic polymorphisms and hypertensive disorders of pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1aju7rE&md5=67f38c885ecc7129032e3d03e7b0bc5bCAS |
American Society for Reproductive Medicine (ASRM) (2012). Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil. Steril. 98, 1103–1111.
| Evaluation and treatment of recurrent pregnancy loss: a committee opinion.Crossref | GoogleScholarGoogle Scholar |
Auton, A., Brooks, L. D., Durbin, R. M., Garrison, E. P., Kang, H. M., Korbel, J. O., Marchini, J. L., McCarthy, S., McVean, G. A., and Abecasis, G. R. (2015). A global reference for human genetic variation. Nature 526, 68–74.
| A global reference for human genetic variation.Crossref | GoogleScholarGoogle Scholar |
Awata, T., Inoue, K., Kurihara, S., Ohkubo, T., Watanabe, M., Inukai, K., Inoue, I., and Katayama, S. (2002). A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51, 1635–1639.
| A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XjtlGmurk%3D&md5=f331abdb7cf9958c087175f414a0a835CAS |
Barrett, J. C., Fry, B., Maller, J., and Daly, M. J. (2005). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265.
| Haploview: analysis and visualization of LD and haplotype maps.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXkt1WitQ%3D%3D&md5=be70cb8299e90fc3a8f6300ce49bcbabCAS |
Bhatnagar, S., Bhattacharjee, J., Vaid, M., Madan, T., Trivedi, S. S., and Sarma, P. U. (2007). Inducible nitric oxide synthase (iNOS) gene polymorphism in pre-eclampsia: a pilot study in North India. Aust. N. Z. J. Obstet. Gynaecol. 47, 477–482.
| Inducible nitric oxide synthase (iNOS) gene polymorphism in pre-eclampsia: a pilot study in North India.Crossref | GoogleScholarGoogle Scholar |
Boquett, J., Schuler-Faccini, L., Jobim, L. F., Jobim, M., Fagundes, N. J., and Hunemeier, T. (2015). Self-assessment of color categories and its relationship with HLA profiling in Brazilian bone marrow donors. Biol. Blood Marrow Transplant. 21, 1140–1144.
| Self-assessment of color categories and its relationship with HLA profiling in Brazilian bone marrow donors.Crossref | GoogleScholarGoogle Scholar |
Burton, G. J., and Jauniaux, E. (2004). Placental oxidative stress: from miscarriage to preeclampsia. J. Soc. Gynecol. Investig. 11, 342–352.
| Placental oxidative stress: from miscarriage to preeclampsia.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXntlentLs%3D&md5=a610e0410ec1c20cc8d317d027cfdaaaCAS |
Burton, G. J., and Jauniaux, E. (2011). Oxidative stress. Best Pract. Res. Clin. Obstet. Gynaecol. 25, 287–299.
| Oxidative stress.Crossref | GoogleScholarGoogle Scholar |
Cardena, M. M., Ribeiro-Dos-Santos, A., Santos, S., Mansur, A. J., Pereira, A. C., and Fridman, C. (2013). Assessment of the relationship between self-declared ethnicity, mitochondrial haplogroups and genomic ancestry in Brazilian individuals. PLoS One 8, e62005.
| Assessment of the relationship between self-declared ethnicity, mitochondrial haplogroups and genomic ancestry in Brazilian individuals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXntFaltL0%3D&md5=53d156b12709966b017d50ac344a0377CAS |
Chwalisz, K., and Garfield, R. E. (2000). Role of nitric oxide in implantation and menstruation. Hum. Reprod. 15, 96–111.
| Role of nitric oxide in implantation and menstruation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXnsFWnsLw%3D&md5=2226dcd06aa6e3d8983dec24e1e1e5ceCAS |
Coulam, C. B., and Jeyendran, R. S. (2008). Vascular endothelial growth factor gene polymorphisms and recurrent pregnancy loss. Am. J. Reprod. Immunol. 59, 301–305.
| Vascular endothelial growth factor gene polymorphisms and recurrent pregnancy loss.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXltlSks7w%3D&md5=c6454fa99cf09eb5ab79666e315eaa1cCAS |
Dutra, C. G., Fraga, L. R., Nacul, A. P., Passos, E. P., Goncalves, R. O., Nunes, O. L., De Godoy, B. A., Leistner-Segal, S., Luiz Vianna, F. S., Schueler-Faccini, L., and Vieira Sanseverino, M. T. (2014). Lack of association between thrombophilic gene variants and recurrent pregnancy loss. Hum. Fertil. (Camb.) 17, 99–105.
| Lack of association between thrombophilic gene variants and recurrent pregnancy loss.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXptlyrt7g%3D&md5=f94f4cb9fd6f3225baaef9f43105da39CAS |
Eller, A. G., Branch, D. W., Nelson, L., Porter, T. F., and Silver, R. M. (2011). Vascular endothelial growth factor-A gene polymorphisms in women with recurrent pregnancy loss. J. Reprod. Immunol. 88, 48–52.
| Vascular endothelial growth factor-A gene polymorphisms in women with recurrent pregnancy loss.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsF2is7fN&md5=6f685da5f5190e6aba53f4b61bc0ccafCAS |
Feodor Nilsson, S., Andersen, P. K., Strandberg-Larsen, K., and Nybo Andersen, A. M. (2014). Risk factors for miscarriage from a prevention perspective: a nationwide follow-up study. BJOG 121, 1375–1385.
| Risk factors for miscarriage from a prevention perspective: a nationwide follow-up study.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC2cvmtVGnsg%3D%3D&md5=80b3b36d7edc0956209924d21c56f7bfCAS |
Ford, H. B., and Schust, D. J. (2009). Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev. Obstet. Gynecol. 2, 76–83.
Fraga, L. R., Boquett, J. A., Dutra, C. G., Vianna, F. S., Heck, C., Goncalves, R. O., Paskulin, D. D., Costa, O. L., Ashton-Prolla, P., Sanseverino, M. T., and Schuler-Faccini, L. (2014a). Interaction between TP63 and MDM2 genes and the risk of recurrent pregnancy loss. Eur. J. Obstet. Gynecol. Reprod. Biol. 182, 7–10.
| Interaction between TP63 and MDM2 genes and the risk of recurrent pregnancy loss.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsV2nsb3J&md5=2403e41b419d2740c85a746edd2f02dbCAS |
Fraga, L. R., Dutra, C. G., Boquett, J. A., Vianna, F. S. L., Goncalves, R. O., Paskulin, D. D., Costa, O. L., Ashton-Prolla, P., Sanseverino, M. T. V., and Schuler-Faccini, L. (2014b). p53 signaling pathway polymorphisms associated to recurrent pregnancy loss. Mol. Biol. Rep. 41, 1871–1877.
| p53 signaling pathway polymorphisms associated to recurrent pregnancy loss.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXptFymug%3D%3D&md5=addc185dd7d2586f374e905e09b5f2b8CAS |
Fu, L., Zhao, Y., Lu, J., Shi, J., Li, C., Liu, H., and Li, Y. (2009). Functional single nucleotide polymorphism-1026C/A of inducible nitric oxide synthase gene with increased YY1-binding affinity is associated with hypertension in a Chinese Han population. J. Hypertens. 27, 991–1000.
| Functional single nucleotide polymorphism-1026C/A of inducible nitric oxide synthase gene with increased YY1-binding affinity is associated with hypertension in a Chinese Han population.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXltVahurY%3D&md5=24203762042c749d6c093c6058265819CAS |
Fujii, J., Iuchi, Y., and Okada, F. (2005). Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reprod. Biol. Endocrinol. 3, 43.
| Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system.Crossref | GoogleScholarGoogle Scholar |
Gonçalves, R. O., Fraga, L. R., Santos, W. V. B., Carvalho, A. F. L., Veloso Cerqueira, B. A. V., Sarno, M., Toralles, M. B. P., Vieira, M. J., Dutra, C. G., Schüler-Faccini, L., Sanseverino, M. T. V., Gonçalves, M. S., Vianna, F. S. L., and Costa, O. L. N. (2016). Association between the thrombophilic polymorphisms MTHFR C677T, Factor V Leiden, and prothrombin G20210A and recurrent miscarriage in Brazilian women. Genet. Mol. Res. 15, gmr.15038156.
| Association between the thrombophilic polymorphisms MTHFR C677T, Factor V Leiden, and prothrombin G20210A and recurrent miscarriage in Brazilian women.Crossref | GoogleScholarGoogle Scholar |
Gray, K. A., Yates, B., Seal, R. L., Wright, M. W., and Bruford, E. A. (2015). Genenames.org: the HGNC resources in 2015. Nucleic Acids Res. 43, D1079–D1085.
| Genenames.org: the HGNC resources in 2015.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXhtVymt7rM&md5=ae5c8e1f36d40287cdab46949fe41d23CAS |
Gupta, S., Agarwal, A., Banerjee, J., and Alvarez, J. G. (2007). The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review. Obstet. Gynecol. Surv. 62, 335–347.
| The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review.Crossref | GoogleScholarGoogle Scholar |
Gurdol, F., Cakmakoglu, B., Dasdemir, S., Isbilen, E., Bekpinar, S., and Isbir, T. (2012). −765 G→C and −1195 A→G promoter variants of the cyclooxygenase-2 gene decrease the risk for preeclampsia. Genet. Test. Mol. Biomarkers 16, 435–438.
| −765 G→C and −1195 A→G promoter variants of the cyclooxygenase-2 gene decrease the risk for preeclampsia.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xns1Sjtb0%3D&md5=170280ce8679f98755587e006c53ffe0CAS |
Hussain, S. P., Hofseth, L. J., and Harris, C. C. (2003). Radical causes of cancer. Nat. Rev. Cancer 3, 276–285.
| Radical causes of cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXisFajtLw%3D&md5=a3a61ab0142af25f08a564b13b951c58CAS |
Ignarro, L. J. (2010). ‘Nitric Oxide: Biology and Pathobiology’. (Elsevier: Amsterdam.)
Kesmodel, U., Wisborg, K., Olsen, S. F., Henriksen, T. B., and Secher, N. J. (2002). Moderate alcohol intake in pregnancy and the risk of spontaneous abortion. Alcohol Alcohol. 37, 87–92.
| Moderate alcohol intake in pregnancy and the risk of spontaneous abortion.Crossref | GoogleScholarGoogle Scholar |
Kumar, S. (2011). Occupational, environmental and lifestyle factors associated with spontaneous abortion. Reprod. Sci. 18, 915–930.
| Occupational, environmental and lifestyle factors associated with spontaneous abortion.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlCnsrvM&md5=9a8d1ecc4db50d485921dda00d267811CAS |
Lambrechts, D., Storkebaum, E., Morimoto, M., Del-Favero, J., Desmet, F., Marklund, S. L., Wyns, S., Thijs, V., Andersson, J., van Marion, I., Al-Chalabi, A., Bornes, S., Musson, R., Hansen, V., Beckman, L., Adolfsson, R., Pall, H. S., Prats, H., Vermeire, S., Rutgeerts, P., Katayama, S., Awata, T., Leigh, N., Lang-Lazdunski, L., Dewerchin, M., Shaw, C., Moons, L., Vlietinck, R., Morrison, K. E., Robberecht, W., Van Broeckhoven, C., Collen, D., Andersen, P. M., and Carmeliet, P. (2003). VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nat. Genet. 34, 383–394.
| VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXmt1Skurk%3D&md5=72b4d9348ba3768b45c7534d0d609687CAS |
Laurino, M. Y., Bennett, R. L., Saraiya, D. S., Baumeister, L., Doyle, D. L., Leppig, K., Pettersen, B., Resta, R., Shields, L., Uhrich, S., Varga, E. A., and Raskind, W. H. (2005). Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors. J. Genet. Couns. 14, 165–181.
| Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors.Crossref | GoogleScholarGoogle Scholar |
Lee, G. S., Joe, Y. S., Kim, S. J., and Shin, J. C. (2010). Cytokine-related genes and oxidation-related genes detected in preeclamptic placentas. Arch. Gynecol. Obstet. 282, 363–369.
| Cytokine-related genes and oxidation-related genes detected in preeclamptic placentas.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFWqu7%2FK&md5=1237091f505fe72df1220aa2c359ff50CAS |
Leite, T. K., Fonseca, R. M., de Franca, N. M., Parra, E. J., and Pereira, R. W. (2011). Genomic ancestry, self-reported “color” and quantitative measures of skin pigmentation in Brazilian admixed siblings. PLoS One 6, e27162.
| Genomic ancestry, self-reported “color” and quantitative measures of skin pigmentation in Brazilian admixed siblings.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsFSiurnK&md5=76c228942bf93a9fda259dc55959493bCAS |
Li, W., Liu, H., Fu, L., Li, D., and Zhao, Y. (2010). Identification of Yin Yang 1-interacting partners at −1026C/A in the human iNOS promoter. Arch. Biochem. Biophys. 498, 119–126.
| Identification of Yin Yang 1-interacting partners at −1026C/A in the human iNOS promoter.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXmslWisr4%3D&md5=ec8e002e86b1ee08c5af43ba4161a026CAS |
Li, L., Donghong, L., Shuguang, W., Hongbo, Z., Jing, Z., and Shengbin, L. (2013). Polymorphisms in the vascular endothelial growth factor gene associated with recurrent spontaneous miscarriage. J. Matern. Fetal Neonatal Med. 26, 686–690.
| Polymorphisms in the vascular endothelial growth factor gene associated with recurrent spontaneous miscarriage.Crossref | GoogleScholarGoogle Scholar |
Lim, H., Paria, B. C., Das, S. K., Dinchuk, J. E., Langenbach, R., Trzaskos, J. M., and Dey, S. K. (1997). Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 91, 197–208.
| Multiple female reproductive failures in cyclooxygenase 2-deficient mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXntVyiu7o%3D&md5=937870333d70de6fa6226cfdf969dccbCAS |
Lins, T. C., Vieira, R. G., Abreu, B. S., Gentil, P., Moreno-Lima, R., Oliveira, R. J., and Pereira, R. W. (2011). Genetic heterogeneity of self-reported ancestry groups in an admixed Brazilian population J. Epidemiol. 21, 240–245.
| Genetic heterogeneity of self-reported ancestry groups in an admixed Brazilian populationCrossref | GoogleScholarGoogle Scholar |
Magdoud, K., Dendana, M., Herbepin, V., Hizem, S., Ben Jazia, K., Messaoudi, S., Almawi, W. Y., Touraine, R., and Mahjoub, T. (2012). Identification of specific vascular endothelial growth factor susceptible and protective haplotypes associated with recurrent spontaneous miscarriages. Hum. Reprod. 27, 1536–1541.
| Identification of specific vascular endothelial growth factor susceptible and protective haplotypes associated with recurrent spontaneous miscarriages.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xmt1Slu78%3D&md5=e11e6935ee5fa2609ba1a74eda0fee2bCAS |
Marions, L., and Danielsson, K. G. (1999). Expression of cyclo-oxygenase in human endometrium during the implantation period. Mol. Hum. Reprod. 5, 961–965.
| Expression of cyclo-oxygenase in human endometrium during the implantation period.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmvFagur0%3D&md5=3313c20cbf034b3afd0e0977a6ab51b2CAS |
Michita, R. T., Bao Zambra, F. M., Fraga, L. R., Vieira Sanseverino, M. T., Callegari-Jacques, S. M., Vianna, P., and Bogo Chies, J. A. (2016). A tug-of-war between tolerance and rejection – new evidence for 3′UTR HLA-G haplotypes influence in recurrent pregnancy loss. Hum. Immunol. 77, 892–897.
| A tug-of-war between tolerance and rejection – new evidence for 3′UTR HLA-G haplotypes influence in recurrent pregnancy loss.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhtFKmtbvE&md5=8f457eb4ecf8b35acb5717b843970467CAS |
Muniz, J. J., Izidoro-Toledo, T. C., Metzger, I. F., Sandrim, V. C., and Tanus-Santos, J. E. (2009). Interethnic differences in the distribution of clinically relevant vascular endothelial growth factor genetic polymorphisms. DNA Cell Biol. 28, 567–572.
| Interethnic differences in the distribution of clinically relevant vascular endothelial growth factor genetic polymorphisms.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtlWhurrN&md5=8d3e77de4af9e54a14dfcb0f43af5cabCAS |
Oliveira-Paula, G. H., Lacchini, R., Coeli-Lacchini, F. B., Junior, H. M., and Tanus-Santos, J. E. (2013). Inducible nitric oxide synthase haplotype associated with hypertension and responsiveness to antihypertensive drug therapy. Gene 515, 391–395.
| Inducible nitric oxide synthase haplotype associated with hypertension and responsiveness to antihypertensive drug therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXkt1amtg%3D%3D&md5=e76e93ef77fbc68ed41c680c6fec2360CAS |
Papazoglou, D., Galazios, G., Papatheodorou, K., Liberis, V., Papanas, N., Maltezos, E., and Maroulis, G. B. (2005). Vascular endothelial growth factor gene polymorphisms and idiopathic recurrent pregnancy loss. Fertil. Steril. 83, 959–963.
| Vascular endothelial growth factor gene polymorphisms and idiopathic recurrent pregnancy loss.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktFGms7Y%3D&md5=fe4f3a9d6f118ce0acba5af434adc756CAS |
Paria, B. C., Reese, J., Das, S. K., and Dey, S. K. (2002). Deciphering the cross-talk of implantation: advances and challenges. Science 296, 2185–2188.
| Deciphering the cross-talk of implantation: advances and challenges.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XkvFGhsbs%3D&md5=f766ba2084acd87343cea325d5cb9e45CAS |
Parra, F. C., Amado, R. C., Lambertucci, J. R., Rocha, J., Antunes, C. M., and Pena, S. D. (2003). Color and genomic ancestry in Brazilians. Proc. Natl. Acad. Sci. USA 100, 177–182.
| Color and genomic ancestry in Brazilians.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXktlOgtg%3D%3D&md5=537729e9219afbd091d25c590aed3d4dCAS |
Pereza, N., Ostojić, S., Smirčić, A., Hodžić, A., Kapović, M., and Peterlin, B. (2015). The −2549 insertion/deletion polymorphism in the promoter region of the VEGFA gene in couples with idiopathic recurrent spontaneous abortion. J. Assist. Reprod. Genet. 32, 1789–1794.
| The −2549 insertion/deletion polymorphism in the promoter region of the VEGFA gene in couples with idiopathic recurrent spontaneous abortion.Crossref | GoogleScholarGoogle Scholar |
Pereza, N., Ostojić, S., Kapović, M., and Peterlin, B. (2017). Systematic review and meta-analysis of genetic association studies in idiopathic recurrent spontaneous abortion. Fertil. Steril. 107, 150–159.e2.
| Systematic review and meta-analysis of genetic association studies in idiopathic recurrent spontaneous abortion.Crossref | GoogleScholarGoogle Scholar |
Pimenta, J. R., Zuccherato, L. W., Debes, A. A., Maselli, L., Soares, R. P., Moura-Neto, R. S., Rocha, J., Bydlowski, S. P., and Pena, S. D. (2006). Color and genomic ancestry in Brazilians: a study with forensic microsatellites. Hum. Hered. 62, 190–195.
| Color and genomic ancestry in Brazilians: a study with forensic microsatellites.Crossref | GoogleScholarGoogle Scholar |
Piranda, D. N., Festa-Vasconcellos, J. S., Amaral, L. M., Bergmann, A., and Vianna-Jorge, R. (2010). Polymorphisms in regulatory regions of cyclooxygenase-2 gene and breast cancer risk in Brazilians: a case-control study. BMC Cancer 10, 613.
| Polymorphisms in regulatory regions of cyclooxygenase-2 gene and breast cancer risk in Brazilians: a case-control study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVeqtLjM&md5=7fc76090da561b7cbad89a02a3e0cbb3CAS |
Rai, R., and Regan, L. (2006). Recurrent miscarriage. Lancet 368, 601–611.
| Recurrent miscarriage.Crossref | GoogleScholarGoogle Scholar |
Renner, W., Kotschan, S., Hoffmann, C., Obermayer-Pietsch, B., and Pilger, E. (2000). 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. 37, 443–448.
| A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXoslGmsQ%3D%3D&md5=cefe24dbe32ea146bb99a0362b5adcb6CAS |
Ruiz-Linares, A., Adhikari, K., Acuna-Alonzo, V., Quinto-Sanchez, M., Jaramillo, C., Arias, W., Fuentes, M., Pizarro, M., Everardo, P., de Avila, F., Gomez-Valdes, J., Leon-Mimila, P., Hunemeier, T., Ramallo, V., Silva de Cerqueira, C. C., Burley, M. W., Konca, E., de Oliveira, M. Z., Veronez, M. R., Rubio-Codina, M., Attanasio, O., Gibbon, S., Ray, N., Gallo, C., Poletti, G., Rosique, J., Schuler-Faccini, L., Salzano, F. M., Bortolini, M. C., Canizales-Quinteros, S., Rothhammer, F., Bedoya, G., Balding, D., and Gonzalez-Jose, R. (2014). Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals. PLoS Genet. 10, e1004572.
| Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.Crossref | GoogleScholarGoogle Scholar |
Saboori, S., Noormohammadi, Z., and Zare-Karizi, S. (2016). Genetic variation in vascular endothelial growth factor gene and its association with recurrent spontaneous abortion. Bratisl. Lek Listy 117, 80–86.
| 1:STN:280:DC%2BC28nmsFGksw%3D%3D&md5=4ca139360ffaa160e47bc685fb2e0730CAS |
Salazar, L. A., Inostroza, M., Jara, C., Vega, F., Garcia, R., Ciuffardi, I., and Guzman, N. (2010). Association of −765G>C polymorphism of the COX-2 gene with recurrent embryo implantation failure in Southern Chilean women. Clin. Chim. Acta 411, 1822–1824.
| Association of −765G>C polymorphism of the COX-2 gene with recurrent embryo implantation failure in Southern Chilean women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFGhtL3I&md5=a166d97cb1f0186a33c6739822b958e0CAS |
Şamlı, H., Demir, B. Ç., Özgöz, A., Atalay, M. A., and Uncu, G. (2012). Vascular endothelial growth factor gene 1154 G/A, 2578 C/A, 460 C/T, 936 C/T polymorphisms and association with recurrent pregnancy losses. Genet. Mol. Res. 11, 4739–4745.
| Vascular endothelial growth factor gene 1154 G/A, 2578 C/A, 460 C/T, 936 C/T polymorphisms and association with recurrent pregnancy losses.Crossref | GoogleScholarGoogle Scholar |
Stephens, M., and Scheet, P. (2005). Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am. J. Hum. Genet. 76, 449–462.
| Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhsFKrsbg%3D&md5=998f87098bae2789d70b8d9d4229c62dCAS |
Stephens, M., Smith, N. J., and Donnelly, P. (2001). A new statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet. 68, 978–989.
| A new statistical method for haplotype reconstruction from population data.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M3kslWgsA%3D%3D&md5=b0efdbdf57b864e237042da7349633bcCAS |
Su, M. T., Lin, S. H., and Chen, Y. C. (2011). Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum. Reprod. Update 17, 803–812.
| Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlejsbrN&md5=f0428f8aa0bcf729873d08e399dc3bd6CAS |
Su, M. T., Lin, S. H., Chen, Y. C., and Kuo, P. L. (2014). Gene–gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss. J. Assist. Reprod. Genet. 31, 699–705.
| Gene–gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.Crossref | GoogleScholarGoogle Scholar |
Traina, E., Daher, S., Moron, A. F., Sun, S. Y., Franchim, C. S., and Mattar, R. (2011). Polymorphisms in VEGF, progesterone receptor and IL-1 receptor genes in women with recurrent spontaneous abortion. J. Reprod. Immunol. 88, 53–57.
| Polymorphisms in VEGF, progesterone receptor and IL-1 receptor genes in women with recurrent spontaneous abortion.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsF2is7fO&md5=c5ab4b14bc3496589b324098cc5c0017CAS |
Wang, S. S., Davis, S., Cerhan, J. R., Hartge, P., Severson, R. K., Cozen, W., Lan, Q., Welch, R., Chanock, S. J., and Rothman, N. (2006). Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. Carcinogenesis 27, 1828–1834.
| Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xotl2ms7k%3D&md5=ab6a60ab56a567ba1ccb794a45ddb264CAS |
Wang, Y., Zhao, A. M., and Lin, Q. D. (2010). Role of cyclooxygenase-2 signaling pathway dysfunction in unexplained recurrent spontaneous abortion. Chin. Med. J. (Engl.) 123, 1543–1547.
| 1:CAS:528:DC%2BC3cXpvFWqt7s%3D&md5=77da8b5f93b94105a5475fcb3c4206c8CAS |
Webster, R. P., Roberts, V. H., and Myatt, L. (2008). Protein nitration in placenta – functional significance. Placenta 29, 985–994.
| Protein nitration in placenta – functional significance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsVWrsLnL&md5=90efa26c33a30331d387b8357c747404CAS |
Wilcox, A. J., Weinberg, C. R., O’Connor, J. F., Baird, D. D., Schlatterer, J. P., Canfield, R. E., Armstrong, E. G., and Nisula, B. C. (1988). Incidence of early loss of pregnancy. N. Engl. J. Med. 319, 189–194.
| Incidence of early loss of pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1c3ns1Snsw%3D%3D&md5=4c1bc2155b67c43026d2a522569765beCAS |
Xing, X., Yan, J., Zhao, Y., You, L., Bian, Y., and Chen, Z. J. (2011). Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women. Am. J. Reprod. Immunol. 65, 521–525.
| Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmvFOks7w%3D&md5=16cfb47cd035d9d19f00b0d1d14fa77cCAS |
Xu, X., Du, C., Li, H., Du, J., Yan, X., Peng, L., Li, G., and Chen, Z. J. (2015). Association of VEGF genetic polymorphisms with recurrent spontaneous abortion risk: a systematic review and meta-analysis. PLoS One 10, e0123696.
| Association of VEGF genetic polymorphisms with recurrent spontaneous abortion risk: a systematic review and meta-analysis.Crossref | GoogleScholarGoogle Scholar |
Zhang, X., Miao, X., Tan, W., Ning, B., Liu, Z., Hong, Y., Song, W., Guo, Y., Zhang, X., Shen, Y., Qiang, B., Kadlubar, F. F., and Lin, D. (2005). Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterology 129, 565–576.
| 1:CAS:528:DC%2BD2MXpvVWmsbw%3D&md5=bc0f27607479435ba34513ff3573220dCAS |
Zhang, B., Dai, B., Zhang, X., and Wang, Z. (2012). Vascular endothelial growth factor and recurrent spontaneous abortion: a meta-analysis. Gene 507, 1–8.
| Vascular endothelial growth factor and recurrent spontaneous abortion: a meta-analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtFakurvN&md5=361806e0c7423df8be33ace26066e468CAS |
