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Генетическая предрасположенность к рецидивирующему течению вульвовагинального кандидоза
Погосян Ш.М., Межевитинова Е.А., Донников А.Е. и др. Генетическая предрасположенность к рецидивирующему течению вульвовагинального кандидоза. Гинекология. 2017; 19 (4): 20–25. DOI: 10.26442/2079-5696_19.4.20-25
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Pogosyan Sh.M., Mezhevitinova E.A., Donnikov A.E. et al. Genetic predisposition to a recurrent course of vulvovaginal candidiasis. Gynecology. 2017;
19 (4): 20–25. DOI: 10.26442/2079-5696_19.4.20-25
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Вульвовагинальный кандидоз (ВВК) зачастую встречается у женщин репродуктивного возраста. У 5–10% женщин ВВК развивается рецидивирующий ВВК (РВВК), который характеризуется развитием 4 и более эпизодов ВВК в течение 12 мес. Есть данные, что наряду с известными факторами риска, такими как антибактериальная терапия, сахарный диабет, беременность, в патогенезе развития РВВК важную роль принадлежит генетическим особенностям пациенток и противогрибковому иммунному ответу. Целью настоящего исследования явилось выявление молекулярно-генетических факторов рецидивирования ВВК. Результаты нашего исследования показали, что однонуклеотидный полиморфизм генов IL4, IL1b и CCL2 ассоциирован с рецидивирующим вульвовагинальным кандидозом и является предрасполагающим фактором для его развития.
Ключевые слова: вульвовагинальный кандидоз, рецидивирующий вульвовагинальный кандидоз (РВВК), предрасположенность к развитию РВВК, полиморфизм генов, генетическая факторы развития РВВК.
Ключевые слова: вульвовагинальный кандидоз, рецидивирующий вульвовагинальный кандидоз (РВВК), предрасположенность к развитию РВВК, полиморфизм генов, генетическая факторы развития РВВК.
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Vulvovaginal candidiasis (VVC) frequently occur in women of childbearing age. 5–10% of these women experience recurrent vulvovaginal candidiasis (RVVC), which is characterized by at least 4 episodes of infection in 12 months. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and antifungal immune response play a substantial role in the pathogenesis of RVVC. The aim of this study was to identify a molecular-genetic factors of recurrence of VVC. Our results shows that single nucleotide polymorphisms (SNP) in cytokine genes such as IL4, IL1b and CCL2 were associated with recurrent vulvovaginal candidiasis and effect on susceptibility to disease.
Key words: vulvovaginal candidiasis, recurrent vulvovaginal candidiasis (RVVC), predisposition to RVVC, gene polymorphism, genetic factors of RVVC.
Полный текст
Список литературы
1. Sherrard J, Donders G, White D. European (IUSTI/WHO) Guideline on the Management of Vaginal Discharge. European STI Guidelines Editorial Board. 2011; p. 1–23.
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4. Sobel JD. Vulvovaginal candidiasis: Epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998; 178 (2): 203–11.
5. Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol 2016; 214 (1): 15–21.
6. Guzel AB, Ilkit M, Burgut R et al. An Evaluation of Risk Factors in Pregnant Women with Candida Vaginitis and the Diagnostic Value of Simultaneous Vaginal and Rectal Sampling. Mycopathologia 2011; 172 (1): 25–36.
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8. Calderon L, Williams R, Martinez M et al. Genetic susceptibility to vaginal candidiasis. Med Mycol 2003; 41 (2): 143–7.
9. Jaeger M, Plantinga TS, Joosten LAB et al. Genetic basis for recurrent vulvo-vaginal candidiasis. Cur Infect Dis Rep 2013; 15 (2): 136–42.
10. Smeekens SP. Genetic susceptibility to Candida infections. EMBO Mol Med 2013; 5 (6): 805–13.
11. Rosentul D. Polymorphism in innate immunity genes and susceptibility to recurrent vulvovaginal candidiasis. J Mycol Med 2009; 19 (3): 191–6.
12. Puel A. Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr Opin Allergy Clin Immunol 2012; 12 (6): 616–22.
13. Babula O, Lazdane G, Kroica J et al. Relation between recurrent vulvovaginal candidiasis, vaginal concentrations of mannose-binding lectin, and a mannose-binding lectin gene polymorphism in Latvian women. Clin Infect Dis 2003; 37 (5): 733–7.
14. Babula O, Lazdane G, Kroica J et al. Frequency of interleukin-4 (IL-4)-589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis. Clin Infect Dis 2005; 40 (9): 1258–62.
15. De Luca A, Carvalho A, Cunha C et al. IL-22 and IDO1 Affect Immunity and Tolerance to Murine and Human Vaginal Candidiasis. PLoS Pathogens 2013; 9 (7).
16. Donders GGG, Babula O, Bellen G et al. Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis. BJOG 2008; 115 (10): 1225–31.
17. Giraldo PC, Babula O, Goncalves AK et al. Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis. Obstet Gynecol 2007; 109: 1123–8.
18. Liu F, Liao Q, Liu Z. Mannose-binding lectin and vulvovaginal candidiasis. Int J Gynaecol Obstet 2006; 92 (1): 43–7.
19. Rosentul DC, Plantinga TS, Oosting M et al. Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. J Infect Dis 2011; 204 (7): 1138–45.
20. Ferwerda B, Ferwerda G, Plantinga TS et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 2009; 361 (18): 1760–7.
21. Glocker E-O, Hennigs A, Nabavi M et al. A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections. N Engl J Med 2009; 361 (18): 1727–35.
22. Nahum A. The biological significance of TLR3 variant, L412F, in conferring susceptibility to cutaneous candidiasis, CMV and autoimmunity. Autoimmun Rev 2012; 11 (5): 341–7.
23. Nahum A, Bates A, Sharfe N, Roifman CM. Association of the lymphoid protein tyrosine phosphatase, R620W variant, with chronic mucocutaneous candidiasis. J Allergy Clin Immunol 2008; 122 (6): 1220–2.
24. Brouwer N, Dolman KM, van Houdt M et al. Mannose-binding lectin (MBL) facilitates opsonophagocytosis of yeasts but not of bacteria despite MBL binding. J Immunol 2008; 180 (6): 4124–32.
25. Neth O, Jack DL, Dodds AW et al. Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000; 68 (2): 688–93.
26. Sharfe N, Shahar M, Roifman CM. An interleukin-2 receptor gamma chain mutation with normal thymus morphology. J Clin Investig 1997; 100 (12): 3036–43.
27. Practice Bulletin Clinical Management Guidelines for Obstetrician – Gynecologists. Obstet Gynecol 2009; 106: 192–202..
28. Mendling W. Guideline: Vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis). Mycoses 2015; 58 (S1): 1–15.
29. Plantinga TS, Johnson MD, Scott WK et al. Human genetic susceptibility to Candida infections. Med Mycol 2012; 1–10.
30. Wójtowicz A, Tissot F, Lamoth F et al. Polymorphisms in tumor necrosis factor-a increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients. Crit Care Med 2014; 42 (4): e304–8.
31. Ouederni M, Sanal O, Ikincioqullari A et al. Clinical features of candidiasis in patients with inherited interleukin 12 receptor b1 deficiency. Clin Infect Dis 2014; 58 (2): 204–13.
32. Naglik JR. Candida Immunity. New J Sci 2014; 2014 (Article ID 390241).
33. Choi EH, Foster CB, Taylor JG et al. Association between chronic disseminated candidiasis in adult acute leukemia and common IL4 promoter haplotypes. J Infect Dis 2003; 187 (7): 1153–6.
34. Corbett JA, Kwon G, Turk J, McDaniel ML. IL-1b induces the coexpression of both nitric oxide synthase and cyclooxygenase by islets of langerhans: Activation of cyclooxygenase by nitric oxide. Biochemistry 1993; 32 (50): 13767–70.
35. Fang FC. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nature reviews. Microbiology 2004; 2 (10): 820–32.
36. Johnson MD, Plantinga TS, Van De Vosse E et al. Cytokine gene polymorphisms and the outcome of invasive candidiasis: A prospective cohort study. Clin Infect Dis 2012; 54 (4): 502–10.
37. Rosentul DC, Delsing CE, Jaeger M et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol 2014; 5: 483.
38. Sun R, Tian W, Xing X. Association of cytokine gene polymorphisms with susceptibility to invasive candidiasis. Genet Mol Res 2015; 14 (142): 6859–64.
2. Sobel JD, Faro S, Force RW et al. Vulvovaginal candidiasis: Epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998; 178 (2): 203–11.
3. Foxman B, Muraglia R, Dietz J-P et al. Prevalence of recurrent vulvovaginal candidiasis in 5 European countries and the United States: results from an internet panel survey. J Lower Genital Tract Dis 2013; 17 (3): 340–5.
4. Sobel JD. Vulvovaginal candidiasis: Epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998; 178 (2): 203–11.
5. Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol 2016; 214 (1): 15–21.
6. Guzel AB, Ilkit M, Burgut R et al. An Evaluation of Risk Factors in Pregnant Women with Candida Vaginitis and the Diagnostic Value of Simultaneous Vaginal and Rectal Sampling. Mycopathologia 2011; 172 (1): 25–36.
7. Mårdh P-A, Rodrigues AG, Genç M et al. Facts and myths on recurrent vulvovaginal candidosis – a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy. Int J STD AIDS 2002; 13 (8): 522–39.
8. Calderon L, Williams R, Martinez M et al. Genetic susceptibility to vaginal candidiasis. Med Mycol 2003; 41 (2): 143–7.
9. Jaeger M, Plantinga TS, Joosten LAB et al. Genetic basis for recurrent vulvo-vaginal candidiasis. Cur Infect Dis Rep 2013; 15 (2): 136–42.
10. Smeekens SP. Genetic susceptibility to Candida infections. EMBO Mol Med 2013; 5 (6): 805–13.
11. Rosentul D. Polymorphism in innate immunity genes and susceptibility to recurrent vulvovaginal candidiasis. J Mycol Med 2009; 19 (3): 191–6.
12. Puel A. Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr Opin Allergy Clin Immunol 2012; 12 (6): 616–22.
13. Babula O, Lazdane G, Kroica J et al. Relation between recurrent vulvovaginal candidiasis, vaginal concentrations of mannose-binding lectin, and a mannose-binding lectin gene polymorphism in Latvian women. Clin Infect Dis 2003; 37 (5): 733–7.
14. Babula O, Lazdane G, Kroica J et al. Frequency of interleukin-4 (IL-4)-589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis. Clin Infect Dis 2005; 40 (9): 1258–62.
15. De Luca A, Carvalho A, Cunha C et al. IL-22 and IDO1 Affect Immunity and Tolerance to Murine and Human Vaginal Candidiasis. PLoS Pathogens 2013; 9 (7).
16. Donders GGG, Babula O, Bellen G et al. Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis. BJOG 2008; 115 (10): 1225–31.
17. Giraldo PC, Babula O, Goncalves AK et al. Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis. Obstet Gynecol 2007; 109: 1123–8.
18. Liu F, Liao Q, Liu Z. Mannose-binding lectin and vulvovaginal candidiasis. Int J Gynaecol Obstet 2006; 92 (1): 43–7.
19. Rosentul DC, Plantinga TS, Oosting M et al. Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. J Infect Dis 2011; 204 (7): 1138–45.
20. Ferwerda B, Ferwerda G, Plantinga TS et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 2009; 361 (18): 1760–7.
21. Glocker E-O, Hennigs A, Nabavi M et al. A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections. N Engl J Med 2009; 361 (18): 1727–35.
22. Nahum A. The biological significance of TLR3 variant, L412F, in conferring susceptibility to cutaneous candidiasis, CMV and autoimmunity. Autoimmun Rev 2012; 11 (5): 341–7.
23. Nahum A, Bates A, Sharfe N, Roifman CM. Association of the lymphoid protein tyrosine phosphatase, R620W variant, with chronic mucocutaneous candidiasis. J Allergy Clin Immunol 2008; 122 (6): 1220–2.
24. Brouwer N, Dolman KM, van Houdt M et al. Mannose-binding lectin (MBL) facilitates opsonophagocytosis of yeasts but not of bacteria despite MBL binding. J Immunol 2008; 180 (6): 4124–32.
25. Neth O, Jack DL, Dodds AW et al. Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000; 68 (2): 688–93.
26. Sharfe N, Shahar M, Roifman CM. An interleukin-2 receptor gamma chain mutation with normal thymus morphology. J Clin Investig 1997; 100 (12): 3036–43.
27. Practice Bulletin Clinical Management Guidelines for Obstetrician – Gynecologists. Obstet Gynecol 2009; 106: 192–202..
28. Mendling W. Guideline: Vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis). Mycoses 2015; 58 (S1): 1–15.
29. Plantinga TS, Johnson MD, Scott WK et al. Human genetic susceptibility to Candida infections. Med Mycol 2012; 1–10.
30. Wójtowicz A, Tissot F, Lamoth F et al. Polymorphisms in tumor necrosis factor-a increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients. Crit Care Med 2014; 42 (4): e304–8.
31. Ouederni M, Sanal O, Ikincioqullari A et al. Clinical features of candidiasis in patients with inherited interleukin 12 receptor b1 deficiency. Clin Infect Dis 2014; 58 (2): 204–13.
32. Naglik JR. Candida Immunity. New J Sci 2014; 2014 (Article ID 390241).
33. Choi EH, Foster CB, Taylor JG et al. Association between chronic disseminated candidiasis in adult acute leukemia and common IL4 promoter haplotypes. J Infect Dis 2003; 187 (7): 1153–6.
34. Corbett JA, Kwon G, Turk J, McDaniel ML. IL-1b induces the coexpression of both nitric oxide synthase and cyclooxygenase by islets of langerhans: Activation of cyclooxygenase by nitric oxide. Biochemistry 1993; 32 (50): 13767–70.
35. Fang FC. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nature reviews. Microbiology 2004; 2 (10): 820–32.
36. Johnson MD, Plantinga TS, Van De Vosse E et al. Cytokine gene polymorphisms and the outcome of invasive candidiasis: A prospective cohort study. Clin Infect Dis 2012; 54 (4): 502–10.
37. Rosentul DC, Delsing CE, Jaeger M et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol 2014; 5: 483.
38. Sun R, Tian W, Xing X. Association of cytokine gene polymorphisms with susceptibility to invasive candidiasis. Genet Mol Res 2015; 14 (142): 6859–64.
________________________________________________
1. Sherrard J, Donders G, White D. European (IUSTI/WHO) Guideline on the Management of Vaginal Discharge. European STI Guidelines Editorial Board. 2011; p. 1–23.
2. Sobel JD, Faro S, Force RW et al. Vulvovaginal candidiasis: Epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998; 178 (2): 203–11.
3. Foxman B, Muraglia R, Dietz J-P et al. Prevalence of recurrent vulvovaginal candidiasis in 5 European countries and the United States: results from an internet panel survey. J Lower Genital Tract Dis 2013; 17 (3): 340–5.
4. Sobel JD. Vulvovaginal candidiasis: Epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998; 178 (2): 203–11.
5. Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol 2016; 214 (1): 15–21.
6. Guzel AB, Ilkit M, Burgut R et al. An Evaluation of Risk Factors in Pregnant Women with Candida Vaginitis and the Diagnostic Value of Simultaneous Vaginal and Rectal Sampling. Mycopathologia 2011; 172 (1): 25–36.
7. Mårdh P-A, Rodrigues AG, Genç M et al. Facts and myths on recurrent vulvovaginal candidosis – a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy. Int J STD AIDS 2002; 13 (8): 522–39.
8. Calderon L, Williams R, Martinez M et al. Genetic susceptibility to vaginal candidiasis. Med Mycol 2003; 41 (2): 143–7.
9. Jaeger M, Plantinga TS, Joosten LAB et al. Genetic basis for recurrent vulvo-vaginal candidiasis. Cur Infect Dis Rep 2013; 15 (2): 136–42.
10. Smeekens SP. Genetic susceptibility to Candida infections. EMBO Mol Med 2013; 5 (6): 805–13.
11. Rosentul D. Polymorphism in innate immunity genes and susceptibility to recurrent vulvovaginal candidiasis. J Mycol Med 2009; 19 (3): 191–6.
12. Puel A. Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr Opin Allergy Clin Immunol 2012; 12 (6): 616–22.
13. Babula O, Lazdane G, Kroica J et al. Relation between recurrent vulvovaginal candidiasis, vaginal concentrations of mannose-binding lectin, and a mannose-binding lectin gene polymorphism in Latvian women. Clin Infect Dis 2003; 37 (5): 733–7.
14. Babula O, Lazdane G, Kroica J et al. Frequency of interleukin-4 (IL-4)-589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis. Clin Infect Dis 2005; 40 (9): 1258–62.
15. De Luca A, Carvalho A, Cunha C et al. IL-22 and IDO1 Affect Immunity and Tolerance to Murine and Human Vaginal Candidiasis. PLoS Pathogens 2013; 9 (7).
16. Donders GGG, Babula O, Bellen G et al. Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis. BJOG 2008; 115 (10): 1225–31.
17. Giraldo PC, Babula O, Goncalves AK et al. Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis. Obstet Gynecol 2007; 109: 1123–8.
18. Liu F, Liao Q, Liu Z. Mannose-binding lectin and vulvovaginal candidiasis. Int J Gynaecol Obstet 2006; 92 (1): 43–7.
19. Rosentul DC, Plantinga TS, Oosting M et al. Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia. J Infect Dis 2011; 204 (7): 1138–45.
20. Ferwerda B, Ferwerda G, Plantinga TS et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 2009; 361 (18): 1760–7.
21. Glocker E-O, Hennigs A, Nabavi M et al. A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections. N Engl J Med 2009; 361 (18): 1727–35.
22. Nahum A. The biological significance of TLR3 variant, L412F, in conferring susceptibility to cutaneous candidiasis, CMV and autoimmunity. Autoimmun Rev 2012; 11 (5): 341–7.
23. Nahum A, Bates A, Sharfe N, Roifman CM. Association of the lymphoid protein tyrosine phosphatase, R620W variant, with chronic mucocutaneous candidiasis. J Allergy Clin Immunol 2008; 122 (6): 1220–2.
24. Brouwer N, Dolman KM, van Houdt M et al. Mannose-binding lectin (MBL) facilitates opsonophagocytosis of yeasts but not of bacteria despite MBL binding. J Immunol 2008; 180 (6): 4124–32.
25. Neth O, Jack DL, Dodds AW et al. Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000; 68 (2): 688–93.
26. Sharfe N, Shahar M, Roifman CM. An interleukin-2 receptor gamma chain mutation with normal thymus morphology. J Clin Investig 1997; 100 (12): 3036–43.
27. Practice Bulletin Clinical Management Guidelines for Obstetrician – Gynecologists. Obstet Gynecol 2009; 106: 192–202..
28. Mendling W. Guideline: Vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis). Mycoses 2015; 58 (S1): 1–15.
29. Plantinga TS, Johnson MD, Scott WK et al. Human genetic susceptibility to Candida infections. Med Mycol 2012; 1–10.
30. Wójtowicz A, Tissot F, Lamoth F et al. Polymorphisms in tumor necrosis factor-a increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients. Crit Care Med 2014; 42 (4): e304–8.
31. Ouederni M, Sanal O, Ikincioqullari A et al. Clinical features of candidiasis in patients with inherited interleukin 12 receptor b1 deficiency. Clin Infect Dis 2014; 58 (2): 204–13.
32. Naglik JR. Candida Immunity. New J Sci 2014; 2014 (Article ID 390241).
33. Choi EH, Foster CB, Taylor JG et al. Association between chronic disseminated candidiasis in adult acute leukemia and common IL4 promoter haplotypes. J Infect Dis 2003; 187 (7): 1153–6.
34. Corbett JA, Kwon G, Turk J, McDaniel ML. IL-1b induces the coexpression of both nitric oxide synthase and cyclooxygenase by islets of langerhans: Activation of cyclooxygenase by nitric oxide. Biochemistry 1993; 32 (50): 13767–70.
35. Fang FC. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nature reviews. Microbiology 2004; 2 (10): 820–32.
36. Johnson MD, Plantinga TS, Van De Vosse E et al. Cytokine gene polymorphisms and the outcome of invasive candidiasis: A prospective cohort study. Clin Infect Dis 2012; 54 (4): 502–10.
37. Rosentul DC, Delsing CE, Jaeger M et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol 2014; 5: 483.
38. Sun R, Tian W, Xing X. Association of cytokine gene polymorphisms with susceptibility to invasive candidiasis. Genet Mol Res 2015; 14 (142): 6859–64.
Авторы
Ш.М.Погосян*, Е.А.Межевитинова, А.Е.Донников, В.Н.Прилепская, О.В.Бурменская, О.С.Непша, А.А.Быстрицкий
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова» Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*shaqpoxos@mail.r
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова» Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*shaqpoxos@mail.r
________________________________________________
Sh.M.Pogosyan*, E.A.Mezhevitinova, A.E.Donnikov, V.N.Prilepskaia, O.V.Burmenskaia, O.S.Nepsha, A.A.Bystritskiy
V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
*shaqpoxos@mail.r
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