Dataset Information

Maternal polymorphic loci of rs1979277 serine hydroxymethyl transferase and rs1805087 5-methylenetetrahydrofolate are correlated with the development of fetal growth restriction: A case-control study.

ABSTRACT:

Background

Key reactions in folate-mediated single-carbon metabolism are regulated by folate cycle enzymes. Violations of the folate cycle may be associated with the occurrence of fetal growth restriction (FGR) in pregnant women.

Objective

To study the relationship between polymorphisms of folate cycle genes in the mother with the development of FGR.

Materials and methods

In this case-control study, 122 pregnant women with FGR and 243 pregnant women with normal newborn weight were enrolled. The polymorphic loci of folate cycle genes including rs1805087 5-methylenetetrahydrofolate (MTR) and rs1979277 serine hydroxymethyl transferase (SHMT1) were examined. The study of polymorphisms was carried out through the TaqMan probe detection method using polymerase chain reaction. Logistic regression was used to analyze the associations of the polymorphisms.

Results

It was established that the T allele rs1979277 of the SHMT1 gene was correlated with the development of FGR within the framework of the allelic (OR = 1.67, 95% CI 1.20-2.33, p perm < 0.01), additive (OR = 1.69, 95% CI 1.20-2.37, p perm < 0.01), dominant (OR = 1.81, 95% CI 1.15-2.87, p perm = 0.01) and recessive (OR = 2.34, 95% CI 1.15-4.73, p perm = 0.01) models. The association of the G rs1805087 allele of the MTR gene with the occurrence of FGR was also identified following the recessive model (OR = 3.01, 95% CI 1.05-8.68, p perm = 0.04).

Conclusion

Our results indicated that maternal polymorphic loci rs1979277 SHMT1 and rs1805087 MTR may be associated with the development of FGR.

SUBMITTER: Efremova O

PROVIDER: S-EPMC8792379 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:High-grade serous (HGS) ovarian cancer accounts for 90% of all ovarian cancer-related deaths. However, factors that drive HGS ovarian cancer tumor growth have not been fully elucidated. In particular, comprehensive analysis of the metabolic requirements of ovarian cancer tumor growth has not been performed. By analyzing The Cancer Genome Atlas mRNA expression data for HGS ovarian cancer patient samples, we observed that six enzymes of the folic acid metabolic pathway were overexpressed in HGS ovarian cancer samples compared with normal ovary samples. Systematic knockdown of all six genes using short hairpin RNAs (shRNAs) and follow-up functional studies demonstrated that serine hydroxymethyl transferase 1 (SHMT1) was necessary for ovarian cancer tumor growth and cell migration in culture and tumor formation in mice. SHMT1 promoter analysis identified transcription factor Wilms tumor 1 (WT1) binding sites, and WT1 knockdown resulted in reduced SHMT1 transcription in ovarian cancer cells. Unbiased large-scale metabolomic analysis and transcriptome-wide mRNA expression profiling identified reduced levels of several metabolites of the amino sugar and nucleotide sugar metabolic pathways, including sialic acid N-acetylneuraminic acid (Neu5Ac), and downregulation of pro-oncogenic cytokines interleukin-6 and 8 (IL-6 and IL-8) as unexpected outcomes of SHMT1 loss. Overexpression of either IL-6 or IL-8 partially rescued SHMT1 loss-induced tumor growth inhibition and migration. Supplementation of culture medium with Neu5Ac stimulated expression of IL-6 and IL-8 and rescued the tumor growth and migratory phenotypes of ovarian cancer cells expressing SHMT1 shRNAs. In agreement with the ovarian tumor-promoting role of Neu5Ac, treatment with Neu5Ac-targeting glycomimetic P-3Fax-Neu5Ac blocked ovarian cancer growth and migration. Collectively, these results demonstrate that SHMT1 controls the expression of pro-oncogenic inflammatory cytokines by regulating sialic acid Neu5Ac to promote ovarian cancer tumor growth and migration. Thus, targeting of SHMT1 and Neu5Ac represents a precision therapy opportunity for effective HGS ovarian cancer treatment.