RELATIONSHIP OF CYTOKINE GENE POLYMORPHISMS TO THE UTERINE SCAR AFTER CESAREAN SECTION


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Abstract

Our previous studies revealed the essential role of local inflammation and neoangiogenic processes in the pathogenesis of uterine scar incompetence after prior cesarean section. Objective. To study associations between the basic morphological signs of uterine scar incompetence and cytokine gene polymorphism. Subjects and methods. The study encompassed 160 patients aged 18 to 45 years with a uterine scar after cesarean section. During repeat cesarean section, the scar was excised and the tissues of the scar and adjacent myometrium were histologically studied. All the patients were divided into 2 groups according to the results of a morphological study of myometrial biopsy specimens: 1) 80 patients with defective scars (DS) of the uterus and 2) 80 with its adequate scars. The polymorphism of the IL-6 (-174 C>G) and IL-10 (-819 C>T and -592 C>A) genes was determined. Results. The morphological study of scar tissue showed that the signs of inflammation and neoangiogenesis had the maximum sensitivity with a high specificity in detecting DS. At the same time, the presence of hematoma or signs of disorganization, by having a high specificity, may be used only as a confirmatory test due to its insufficient sensitivity. A study of the distribution of IL-6 alleles and genotypes revealed no significant associations with the status of a scar. An analysis of IL-10 haplotype (-819 C>T and-592 C>A) revealed that in the presence of inflammation, the genotypic frequency of the TA allele was 39 versus 17% in the absence of inflammation (OR=3.02 (1.25—7.29), р=0.01). Scar tissue neoangiogenesis was also more common in carriers of the TA allele (OR=2.55 (1.0— 6.50), p=0.05). Conclusion. The allelic variants of the IL-10 gene were shown to be associated with the formation of DS of the uterus after cesarean section.

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About the authors

G. T SUKHIKH

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

A. E DONNIKOV

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

M. I KESOVA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: m_kesova@oparina4.ru

N. E KAN

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

E. A KOGAN

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

T. A DEMURA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

I. V KLIMANTSEV

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

E. Yu AMIRASLANOV

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

M. V SANNIKOVA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

N. A LOMOVA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

O. A SERGUNINA

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

D. D ABRAMOV

ZAO "DNA-Technology Ltd", Moscow

V. V KADOCHNIKOVA

ZAO "DNA-Technology Ltd", Moscow

D. Yu TROFIMOV

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

References

  1. Кофиади И.А., Ребриков Д.В. Методы детекции однонуклеотидных полиморфизмов: аллель-специфичная ПЦР и гибридизация с олигонуклеотидной пробой // Генетика. 2006. — Т. 42, № 1. — С. 22—32.
  2. Сухих Г.Т., Коган Е.А., Демура Т.А.и др. Дезорганизация соединительной ткани в рубцах матки и полиморфизм гена эстрогенового рецептора альфа у пациенток с недифференцированными формами дисплазии соединительной ткани // Акуш. и гин. — 2010. — № 3. — С. 27—31.
  3. Сухих Г.Т., Коган Е.А., Кесова М.И. и др. Морфологические и молекулярно-генетические особенности неоангиогенеза в рубце матки у пациенток с недифференцированной дисплазией соединительной ткани // Акуш. и гин. — 2010. — № 6. — С. 23—28.
  4. Barrett J.C., Fry B., Maller J., Daly M.J. Haploview: analysis and visualization of LD and haplotype maps // Bioinformatics. — 2005. — Vol. 21, № 2. — P. 263—265.
  5. Chen B., Wilkening S., Drechsel M., Hemminki K. SNP_tools: A compact tool package for analysis and conversion of genotype data for MS-Excel // BMC Res. Notes. —2009. — Vol. 2. — P. 214.
  6. Costeas P.A., Koumouli A., Giantsiou-Kyriakou A. et al. Th2 / Th3 cytokine genotypes are associated with pregnancy loss // Hum. Immunol. — 2004. — Vol. 65, № 2. — P. 135—141.
  7. Crilly A., Hamilton J., Clark C. J. et al. Analysis of the 5’ flanking region of the interleukin 10 gene in patients with systemic sclerosis // Rheumatology. — 2003. — Vol. 42, № 11. — P. 1295—1298.
  8. D'Alfonso S., Rampi M., Rolando V. et al. New polymorphisms in the IL-10 promoter region // Genes Immun. — 2000. — Vol. 1, № 3. — P. 231—233.
  9. de Craen A.J., Posthuma D., Remarque E.J. et al. Heritability estimates of innate immunity: an extended twin study // Genes Immun. — 2005. — Vol. 6, № 2. — P. 167—170.
  10. Koss K., Satsangi J., Fanning G.C. et al. (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies // Genes Immun. — 2000. — Vol. 1, № 3. — P. 185—190.
  11. Lyon E. Mutation detection using fluorescent hybridization probes and melting curve analysis // Expert Rev. Mol. Diagn. — 2001. — Vol. 1, № 1. — P. 92—101.
  12. Mysliwska J., Zorena K., Mysliwiec M. et al. The -174GG interleukin-6 genotype is protective from retinopathy and nephropathy in juvenile onset type 1 diabetes mellitus // Pediatr. Res. — 2009. — Vol. 66, № 3. — P. 341—345.
  13. Perrey C., Pravica V., Sinnott P.J., Hutchinson I.V. Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factoralpha genes: a technical report // Transplant. Immunol. — 1998. — Vol. 6, № 3. — P. 193—197.
  14. Reuss E., Fimmers R., Kruger A. et al. Differential regulation of interleukin-10 production by genetic and environmental factors-- a twin study // Genes Immun. — 2002. — Vol. 3, № 7. — P. 407—413.
  15. Temple S.E., Lim E., Cheong K.Y. et al. Alleles carried at positions -819 and -592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae // Immunogenetics. — 2003. — Vol. 55, № 9. — P. 629—632.
  16. Tischendorf J.J., Yagmur E., Scholten D. et al. The interleukin-6 (IL-6)-174 G/C promoter genotype is associated with the presence of septic shock and the ex vivo secretion of IL6 // Int. J. Immunogenet. — 2007. — Vol. 34, № 6. — P. 413—418.

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