Biopolym. Cell. 2011; 27(3):206-213.
http://dx.doi.org/10.7124/bc.0000BB
Molecular Biomedicine
Study on association of the polymorphic variants of ACE (I/D), AT2R1 (A1166C), TNF-α (G308A), MTHFR (C677T) genes and their combinations with the risk of development of perinatal pathology and gestation reduction
1, 3Gorovenko N. G., 1, 2Kyryachenko S. P., 2, 3Rossokha Z. I.
  1. P. L. Shupik National medical academy of post-graduate education
    9, Dorohozhytska Str., Kyiv, Ukraine, 04112
  2. Reference-center of molecular diagnostic MH of Ukraine
    9, Dorohozhytska Str., Kyiv, Ukraine, 04112
  3. State Organization of Genetic and Regenerative Medicine NAMS Ukraine
    67, Vyshhorodska Str., Kyiv, Ukraine, 04114

Abstract

Aim. To study the association of the polymorphic variants of ACE (I/D), AT2R1 (A1166C), TNF-α (G308A), MTHFR (C677T) genes and their combinations with the risk of perinatal pathology and gestation reduction. Methods. The polymorphic variants of genes were analyzed by PCR and RFLP in 235 newborns with severe perinatal pathology and 110 clinically healthy term newborns. Results. An increased risk of severe perinatal pathology was associated with such genotypes: DD and ID (ACE), 1166AC, 1166CC (AT2R1), 677CT (MTHFR), 308AA and 308AG (TNF-α), this risk for homozygotes is almost 2-fold higher than for heterozygotes. Reduction of terms of gestation is associated with the genotype 677TT (MTHFR), and resistance to diseases in the perinatal period – with the genotype II (ACE) and 1166AA (AT2R1), 677CC (MTHFR) and the 308GG (TNF-α), particularly when combined. Conclusions. The identified associations evidence the role of polymorphic variants of ACE, AT2R1, TNF-α, MTHFR genes in the development of severe perinatal pathology and can be used for its early prediction with subsequent correction of treatment.
Keywords: perinatal pathology, polymorphism, ACE, AT2R1, TNF-α, MTHFR genes
Full text: (PDF, in English) (PDF, in Russian)

References

[1] Miller S. P., Wu Y. W., Lee J., Lammer E. J., Iovannisci D. M., Glidden D. V., Bonifacio S. L., Collins A., Shaw G. M., Barkovich A. J., Ferriero D. M. Candidate gene polymorphisms do not differ between newborns with stroke and normal controls Stroke 2006 37, N 11 P. 2678–2683.
[2] Rubens C. E., Gravett M. G., Victora C. G., Nunes T. M., GAPPS Review Group. Global report on preterm birth and stillbirth (7 of 7): mobilizing resources to accelerate innovative solutions (Global Action Agenda) BMC Pregnancy Childbirth 2010 10, Suppl 1 P. S7.
[3] Gorovenko N. G., Kyryachenko S. P., Rossokha Z. I. Association of 677TT polymorphic variant methylentetrahydropholatreductase gene to reduced duration of gestation and development of perinatal pathology of newborn Pediatriya, Akusherstvo i Ginekologiya 2010 72, N 6 P. 15–20.
[4] Gorovenko N. G., Kyryachenko S. P., Rossokha Z. I. The role of G308A polymorphism of TNF-a gene in the development of perinatal pathology in newborns Zdorovie zhenshchiny 2010 N 5 P. 180–184.
[5] Gorovenko N. G., Kyryachenko S. P., Rossokha Z. I. Association of ACE and AT2R1 genes polymorphic variants with the development of perinatal pathology in newborns Medychni Perspektyvy 2010 15, N 4 P. 28–33.
[6] Lechin M., Miguel A., Quinones M., Omran A., Hill R., Yu Q.-T., Rakowski H., Wigle D., Liew C. C., Sole M., Roberts R., Marian A. J. Angiotensin-I converting enzyme genotypes and left ventricular hypertrophy in patients with hypertrophic cardiomyopatthy Circulation 1995 92, N 7 P. 1808–1812.
[7] Bokodi G., Treszl A., Derzbach L., Balogh A., Vasarhelyi B. The association of the carrier state of the tumor necrosis factor-alpha (TNFalpha)-308A allele with the duration of oxygen supplementation in preterm neonates Eur. Cytokine Netw 2005 16, N 1 P. 78–80.
[8] Weisberg I., Tran P., Christensen B., Sibani S., Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity Mol. Genet. Metab 1998 64, N 3 P. 169–172.
[9] Eliseeva Yu. E. Angiotensin-converting enzyme and its physiological role Vopr. Med. Khim 2001 47, N 1 P. 43–54.
[10] Ivanova M. V., Sidorov A. G., Filimonenkova V. A. Role of endothelial dysfunction in the development of multiple organ failure in newborns with perinatal hypoxia Suchasna Pediatriya 2006 10 P. 148–151.
[11] Minushkina L. O., Zateyschikov D. A., Kudryashov O. Endothelial dysfunction: association with polymorphism of the gene receptor (type 1) angiotensin II in patients with coronary heart disease Kardiologiia 2000 12, N 1 P. 101–106.
[12] Shunko E., Konchakovskaya T. The role of TNF-a, IL-1b and IL-6 in hypoxic-ischemic central nervous system of newborns Pediatriya, Akusherstvo i Ginekologiya 2002 N 1 P. 15–19.
[13] Simbirtsev A. S., Gromova A. Yu. Functional gene polymorphisms of the molecules regulating inflammation Cytokines and Inflammation. 2005 4, N 1 P. 3–10.
[14] Beskorovainaya T. S., Gudzenko S., Tverskaya S. M., Poliakov A. V. Association of polymorphic alleles of folate genes exchange with habitual miscarriage Problemy Reproduktsii 2006 N 1 P. 53–60.