The study of the association of polymorphic loci of the folate cycle genes with the development of the 2-3-degree fetal growth restriction syndrome
Background: Folate cycle enzymes regulate key reactions in folate-mediated single-carbon metabolism. The folate cycle disturbances may be associated with the occurrence of placental insufficiency with fetal growth restriction syndrome (FGRS) in pregnant women, however, to date, the relationship of polymorphism of the folate cycle genes with the development of pregnancy pathology has not been examined in sufficient detail. The aim of the study: To study the association of polymorphic loci of the folate cycle genes with the development of 2-3-degree FGRS. Materials and methods: The sample for the study included 112 pregnant women with 2-3-degree FGRS and 243 pregnant women with normal birth weight. The polymorphic loci of the folate cycle gene rs1805087 of the MTR gene were studied, rs1801394 of the MTRR gene, rs1979277 of the SHMT1 gene, rs699517 of the TYMS gene, rs2790 of the TYMS gene involved in the formation of placental insufficiency and FGRS of the 2nd or 3rd degrees. The study was carried out by PCR using the appropriate oligonucleotide primers and probes, followed by analysis of polymorphisms by the detection method of TaqMan probes (real-time PCR). Association analysis was performed using gPLINK v2.050 software. Intergenic interactions in two- and three-locus models were analyzed using MDR method and its GMDR modifications. Results: It was shown that the T allele rs1979277 of the SHMT1 gene is associated with the development of 2-3-degree FGRS in the framework of additive (OR = 1.56, 95% Cl 1,10 - 2,22, p = 0,012, pperm = 0.011) and recessive (OR = 2.55, 95% Cl 1.24-5.22, p = 0,011, pperm = 0.007) models. The association of the G rs1805087 allele of the MTR gene with the formation of 2-3-degree FGRS was revealed in accordance with the recessive model (OR = 3.28, 95% Cl 1.14-9.47, p = 0.028, pperm = 0.014). Two 2-locus and one three-locus models of SNPxSNP interactions associated with the development of FGRS 2-3 degrees were identified. Significant models include three polymorphic loci – rs1979277 SHMT1, rs1805087 MTR, and rs1801394 MTRR. Pairwise interaction rs1801394 MTRR x rs1979277 SHMT1 is the basis of the two most significant models of gene-gene interactions associated with the development of FGRS of 2-3 degrees. Conclusion: Polymorphic loci rs1979277 SHMT1, rs1805087 MTR and rs1801394 MTRR are associated with the development of FGRS of 2-3 degrees.
Efremova OA. The study of the association of polymorphic loci of the folate cycle genes with the development of the 2-3-degree fetal growth restriction syndrome. Research Results in Biomedicine. 2020;6(1):37-50. (In Russian) DOI: 10.18413/2658-6533-2020-6-1-0-4
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