Article Abstract

Methylenetetrahydrofolate reductase polymorphisms at 3'-untranslated region are associated with susceptibility to preterm birth

Authors: Qin Zhu, Ying Chen, Jianrong Dai, Benjing Wang, Minjuan Liu, Yun Wang, Jianying Tao, Hong Li

Abstract

Background: Etiology and mechanism of preterm birth (PTB) is complicated. Genetic susceptibility is one of the key factors involved in the pathogenic mechanism underlying PTB.
Methods: A subset of single nucleotide polymorphisms (SNPs) selected by bioinformatics approach from 3'-untranslated region (3'-UTR) of methylenetetrahydrofolate reductase (MTHFR) gene were subjected to SNaPshot analysis in a case-control study. Three SNPs (rs45451599, rs1537515, rs1537516) were simultaneously tested in one tube, among 1,135 DNA samples including 480 PTBs and 655 term controls.
Results: Two perfectly correlated (r2=1) SNPs, rs1537515 and rs1537516, were found significantly associated with PTB susceptibility [P=0.012; OR: 0.65; 95% confidence interval (CI), 0.47-0.91]. The frequencies of the minor alleles were lower in PTB cases than in controls, which the frequencies were 0.066 in PTB cases and 0.095 in controls. G and T allele frequencies of rs1537515 were the same with rs1537516 (P=0.011; OR: 0.666; 95% CI, 0.49-0.91). Rs45451599 was not found associated with PTB (P=0.52; OR: 0.76; 95% CI, 0.33-1.74). The 18-25 nucleotides in length of microRNAs (miRNAs) which can regulate gene expressions are involved in binding partial complementary sequences within 3'-UTR. The two loci are at 3'-UTR of MTHFR mRNA. Rs1537516 is a potential target of miR-1304-3p, while rs1537515 is miR-1224-3p and miR-3150-5p.
Conclusions: In conclusion, rs1537515 and rs1537516 within the 3'-UTR of the MTHFR gene may be associated with susceptibility to PTB.

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