TSitologiya i Genetika 2019, vol. 53, no. 3, 65-71
Cytology and Genetics 2019, vol. 53, no. 3, 233–238, doi: https://www.doi.org/10.3103/S0095452719030083

Evaluation of the role of polymorphism rs2010963 of VEGF gene in the development of rosaсea and its relationship with clinical forms of the disease

Babajanov O.A., Karimov Ch.Ya., Arifov S.S., Boboev K.T.

SUMMARY. The frequency of genotypic variants of the rs2010963 polymorphism of the gene for vascular endothelial growth factor (VEGF) was analyzed in 140 patients with rosacea in 145 conditionally healthy persons of Uzbek nationality. It was shown that the distribution of genotypes in the studied groups corresponded to the Hardy-Weinberg equilibrium (p > 0,05). Significant differences in the frequency of occurrence for rs2010963 alleles of the VEGF gene were found between groups of patients with rosacea with different clinical forms of the disease and a group of conditionally healthy individuals (P < 0,05). Carrying a functionally unfavorable allele 634C VEGF in the hetero- or homozygous variant significantly increases the risk of developing rosacea. The data obtained indicate the association of this DNA locus with the formation of rosacea in the Uzbek population.

Keywords: rosacea, erythematous form, papulopustular form, VEGF gene, rs2010963 polymorphism

TSitologiya i Genetika
2019, vol. 53, no. 3, 65-71

Current Issue
Cytology and Genetics
2019, vol. 53, no. 3, 233–238,
doi: 10.3103/S0095452719030083

Full text and supplemented materials

Free full text: PDF  

References

1. Karpouzis, A., Avgeridis, P., Tripsianis, G., Gatzidou, E., Kourmouli, N., and Veletza, S., Assessment of tachykinin receptor 3’ gene polymorphism rs3733631 in rosacea, Int. Sch. Res. Notices, 2015. https://doi.org/10.1155/2015/469402

2. Woo, Y.R., Lim, J.H., Cho, D.H., and Park, H.J., Rosacea: molecular mechanisms and management of a chronic cutaneous inflammatory condition, Int. J. Mol. Sci., 2016, vol. 17, no. 9. https://doi.org/10.3390/ijms17091562

3. Spoendlin, J., Voegel, J.J., Jick, S.S., and Meier, C.R., A study on the epidemiology of rosacea in the U.K., Br. J. Dermatol., 2012, vol. 167, no. 3, pp. 598–605. https://doi.org/10.1111/j.1365-2133.2012.11037.x

4. Gravina, A.G., Federico, A., Ruocco, E., Schiavo, A., Masarone, M., Tuccillo, C., Peccerillo, F., Miranda, A., Romano, L., De Sio, C., De Sio, I., Persico, M., Ruocco, V., Riegler, G., Loguercio, C., and Romano, M., Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea, United Eur. Gastroenterol. J., 2015, vol. 3, pp. 17–24. https://doi.org/10.1177/2050640614559262

5. Casas, C., Paul, C., Lahfa, M., Livideanu, B., Lejeune, O., Alvarez-Georges, S., Saint-Martory, C., Degouy, A., Mengeaud, V., Ginisty, H., Durbise, E., Schmitt, A.M., and Redoule, D., Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation, Exp. Dermatol., 2012, vol. 21, no. 12, pp. 906–910. https://doi.org/10.1111/exd.12030

6. Forton, F.M., Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link, J. Eur. Acad. Dermatol. Venereol., 2012, vol. 26, no. 1, pp. 19–28. https://doi.org/10.1111/j.1468-3083.2011.04310.x

7. Cribier, B., Rosacea under the microscope: characteristic histological findings, J. Eur. Acad. Dermatol. Venereol., 2013, vol. 27, no. 11, pp. 1336–1343.

8. Weinstock, L.B. and Steinhoff, M., Rosacea and small intestinal bacterial overgrowth: prevalence and response to rifaximin, J. Am. Acad. Dermatol., 2013, vol. 68, no. 5, pp. 875–876. doi 10.1016/j.jaad.2012.11.038

9. Chen, Y., Moore, C.D., Zhang, J.Y., Hall, R.P., MacLeod, A.S., and Liedtke, W., TRPV4 moves toward center-fold in rosacea pathogenesis, J. Invest. Dermatol., 2017, vol. 137, no. 4, pp. 801–804. https://doi.org/10.1016/j.jid.2016.12.013

10. Nikolakis, G. and Zouboulis, C.C., Skin and glucocorticoids: effects of local skin glucocorticoid impairment on skin homeostasis, Exp. Dermatol., 2014, vol. 23, no. 11, pp. 807–808. https://doi.org/10.1111/exd.12519

11. Nikolakis, G., Stratakis, C.A., Kanaki, T., Slominski, A., and Zouboulis, C.C., Skin steroidogenesis in health and disease, Rev. Endocr. Metab. Disord., 2016, vol. 17, no. 3, pp. 247–258. https://doi.org/10.1007/s11154-016-9390-z

12. Yamasaki, K., Nardo, A.D., Bardan, A., Murakami, M., Ohtake, T., Coda, A., Dorschner, R.A., Bonnart, C., Descargues, P., Hovnanian, A., Morhenn, V.B., and Gallo, R.L., Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea, Nat. Med., 2007, vol. 13, no. 8, pp. 975–980. https://doi.org/10.1038/nm1616

13. Chang, A.L.S., Raber, I., Xu, J., Li, R., Spitale, R., Chen, J., Kiefer, A.K., Tian, C., Eriksson, N.K., Hinds, D.A., and Tung, J.Y., Assessment of the genetic basis of rosacea by genome-wide association study, J. Invest. Dermatol., 2015, vol. 135, no. 6, pp. 1548–1555. https://doi.org/10.1038/jid.2015.53

14. Aldrich, N., Gerstenblith, M., Fu, P., Tuttle, M.S., Varma, P., Gotow, E., Cooper, K.D., Mann, M., and Popkin, D.L., Genetic vs environmental factors that correlate with rosacea: a cohort-based survey of twins, JAMA Dermatol., 2015, vol. 151, no. 11, pp. 1213–1219. https://doi.org/10.1001/jamadermatol.2015.2230

15. Abram, K., Silm, H., Maaroos, H.I., and Oona, M., Risk factors associated with rosacea, J. Eur. Acad. Dermatol. Venereol., 2010, vol. 24, no. 5, pp. 565–571. doi 10.1111 / j.1468-3083.2009.03472.x

16. Steinhoff, M., Schauber, J., and Leyden, J.J., New insights into rosacea pathophysiology: a review of recent findings, J. Am. Acad. Dermatol., 2013, vol. 69, no. 6, pp. 15–26. https://doi.org/10.1016/j.jaad.2013.04.045

17. Vincenti, V., Cassano, C., Rocchi, M., and Persico, G., Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3, Circulation, 1996, vol. 93, no. 8, pp. 1493–1495.

18. Brogan, I.J., Khan, N., Isaac, K., Hutchinson, J.A., Pravica, V., and Hutchinson, I.V., Novel polymorphisms in the promoter and 5' UTR regions of the human vascular endothelial growth factor gene, Hum. Immunol., 1999, vol. 60, pp. 1245–1249. https://doi.org/10.1016/S0198-8859(99)00132-9

19. Watson, C.J., Webb, N.J., Bottomley, M.J., and Brenchley, P.E., Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production, Cytokine, 2000, vol. 12, pp. 1232–1235. https://doi.org/10.1006/cyto.2000.0692

20. Amato, R.J., The effect of genetic diversity on angiogenesis, Exp. Cell Res., 2005, vol. 312, pp. 561–574. https://doi.org/10.1016/j.yexcr.2005.10.021

21. Yamasaki, K. and Gallo, R.L., The molecular pathology of rosacea, J. Dermatol. Sci., 2009, vol. 55, no. 2, pp. 77–81. https://doi.org/10.1016/j.jdermsci.2009.04.007

22. Smith, J.R., Lanier, V.B., Braziel, R.M., Falkenhag, K.M., White, C., and Rosenbaum, J.T., Expression of vascular endothelial growth factor and its receptors in rosacea, Br. J. Ophthalmol., 2007, vol. 91, no. 2, pp. 226–229. doi 10.1136/bjo.2006.101121

23. Jain, L., Craig, A., Vargo, Romano., Danesi, Tristanm., Sissung, Douglask., Price, David., Venzon, Jurgen., Venitz, William., and Figg, D., The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors, Mol. Cancer Ther., 2009, vol. 8, no. 9, pp. 2496–2508. https://doi.org/10.1158/1535-7163.MCT-09-0302

24. Al-Habboubi, H.H., Sater, M.S., Almawi, A.W., Al-Khateeb, G.M., and Almawi, W.Y., Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population, Eur. Cytokine Netw., 2011, vol. 22, no. 3, pp. 154–158.

25. Al-Khateeb, G.M., Mustafa, F.E., Sater, M.S., and Almawi, W.Y., Effect of the functional VEGFA-583C/on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage, Fertil. Steril., 2011, vol. 95, no. 8, pp. 2471–2473. https://doi.org/10.1016/j.fertnstert.2011.03.010

26. Almawi, W.Y., Saldanha, F.L., Mahmood, N.A., Al-Zaman, I., Sater, M.S., and Mustafa, F.E., Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage, Hum. Reprod., 2013, vol. 28, no. 10, pp. 2628–2635. https://doi.org/10.1093/humrep/det308

27. Wang, M., Zhou, X., Zhang, H., Liu, R., And Xu, N., Associations of the VEGF level, VEGF Rs2010963 G/C gene polymorphism and ankylosing spondylitis risk in a Chinese Han population, Immunol. Lett., 2016, vol. 179, pp. 56–60. https://doi.org/10.1016/j.imlet.2016.09.003

28. Do Espírito Santo, G.F., Galera, B.B., Duarte, E.C., Chen, E.S., Azis, L., Damazo, A.S., Saba, G.T., De Sousa Gehrke, F., Guerreiro Da Silva, I.D., and Waisberg, J., Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients, World J. Gastrointest. Oncol., 2017, vol. 9, no. 2, pp. 78–86. https://doi.org/10.4251/Wjgo.V9.I2.78

29. Zidi, S., Stayoussef, M., Gazouani, E., Mezlini, A., Yacoubi-Loueslati, B., and Almawi, W.Y., Relationship of common vascular endothelial growth factor polymorphisms and haplotypes with the risk of cervical cancer in Tunisians, Cytokine, 2015, vol. 74, no. 1, pp. 108–112. https://doi.org/10.1016/j.cyto.2014.11.009

30. Riera, P., Virgili, A.C., Salazar, J., Sebio, A., Tobena, M., Sullivan, I., and Páez, D., Genetic variants in the VEGF pathway as prognostic factors in stages II and III colon cancer, Pharmacogenomics J., 2018, vol. 18, no. 4, pp. 556–564. https://doi.org/10.1038/s41397-017-0009-x

31. Wang, Y., Huang, Q., Liu, J., Wang, Y., Zheng, G., Lin, L., Yu, H., Tang, W., and Huang, Z., Vascular endothelial growth factor a polymorphisms are associated with increased risk of coronary heart disease: a meta-analysis, Oncotarget, 2017, vol. 8, no. 18, pp. 30539–30551. https://doi.org/10.18632/oncotarget.15546

32. Henidi, B., Kaabachi, W., Naouali, A., Kaabachi, S., Zhioua, A., Haj, Sassif., and Hamzaoui, K., Vascular endothelial growth factor (–460 C/T, +405 G/C, and +936 C/T) polymorphisms and endometriosis risk in Tunisian population, Syst. Biol. Reprod. Med., 2015, vol. 61, no. 4, pp. 238–244. https://doi.org/10.3109/19396368.2015.1041622

33. Cardoso, J.V., Abrao, M.S., Vianna-Jorge, R., Ferrari, R., Berardo, P.T., Machado, D.E., and Perini, J.A., Combined effect of vascular endothelial growth factor and its receptor polymorphisms in endometriosis: a case-control study, Eur. J. Obstet. Gynecol. Reprod. Biol., 2017, vol. 209, pp. 25–33. https://doi.org/10.1016/j.ejogrb.2016.10.046

34. Han, L., Zhang, L., Xing, W., Zhuo, R., Lin, X., Hao, Y., Wu, Q., and Zhao, J., The associations between VEGF gene polymorphisms and diabetic retinopathy susceptibility: a meta-analysis of 11 case-control studies, J. Diabetes Res., 2014, vol. 2014. https://doi.org/10.1155/2014/805801

35. Pabst, S., Karpushova, A., Diaz-Lacava, A., Herms, S., Walier, M., Zimmer, S., Cichon, S., Nickenig, G., Nöthen, M.M., Wienker, T.F., and Grohé, C., VEGF gene haplotypes are associated with sarcoidosis, Chest, 2010, vol. 137, no. 1, pp. 156–163. https://doi.org/10.1378/chest.09-1003

36. Al-Khurji, A.F., The role of vascular endothelial growth factor gene polymorphisms in recurrent spontaneous abortions in Saudi women, J. Immun. Biol., 2017, vol. 2, p. 120. https://doi.org/10.4172/2476-1966.1000120

37. Qi, M., Huang, X., Zhou, L., and Zhang, J., Four polymorphisms of VEGF (+405C>G, –460T>C, –2578C>A, and –1154G>A) in susceptibility to psoriasis: a meta-analysis, DNA Cell Biol., 2014, vol. 33, no. 4, pp. 234–244. https://doi.org/10.1089/dna.2013.2252

38. Lee, Y.H. and Song, G.G., Vascular endothelial growth factor gene polymorphisms and psoriasis susceptibility: a meta-analysis, Genet. Mol. Res., 2015, vol. 14, no. 4, pp. 14396–14405. https://doi.org/10.4238/2015.November.18.3

39. Bozduman, T., Evans, S.E., Karahan, S., Hayran, Y., Akbiyik, F., and Lay, I., Genetic risk factors for psoriasis in Turkish population: –1540 C/A, –1512 Ins18, and +405 C/G polymorphisms within the vascular endothelial growth factor gene, Ann. Dermatol., 2016, vol. 28, no. 1, pp. 30–39. https://doi.org/10.5021/ad.2016.28.1.30

40. Sudhesan, A., Rajappa, M., Chandrashekar, L., Ananthanarayanan, P.H., Thappa, D.M., Satheesh, S., and Chandrasekaran, A., Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils, Hum. Immunol., 2017, vol. 78, no. 10, pp. 657–663. https://doi.org/10.1016/j.humimm.2017.08.004