Association of polymorphic loci of the matrix metalloproteinase genes with the development of fetal growth retardation: A case-control study.

BACKGROUND

Matrix metalloproteinases (MMPs) play a crucial role in successful pregnancy as molecular regulatory factors of the developing organism. Additional studies focusing on MMPs activity and function in fetal growth retardation (FGR) may help in the search for diagnostic markers of this pregnancy complication.

OBJECTIVE

To study the association of MMPs gene polymorphisms with the development of FGR.

MATERIALS AND

METHODS

This case-control study included 122 pregnant women with FGR and 243 pregnant women with normal birth weight. We studied polymorphic loci of metalloproteinase genes: rs1799750 of MMP-1, rs243865 of MMP-2, rs3025058 of MMP-3, rs11568819 of MMP-7, rs17577 of MMP-9. The polymorphism study was performed by TaqMan probe detection using real-time precipitation reaction. The logistic regression method was used to analyze the association of polymorphisms with FGR.

RESULTS

The T allelic variant rs243865 of the MMP-2 gene was found to be associated with the development of FGR under allelic (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.08-2.24, pperm = 0.016), additive (OR = 1.53, 95% CI: 1.07-2.18, pperm = 0.015) and dominant (OR = 1.61, 95% CI: 1.03-2.50, pperm = 0.027) models. The FGR-causative locus rs243865 of MMP-2 is located in the enhancer region in the amnion and placenta tissues, affects epigenetic modifications in FGR-significant cell/organ cultures both in the embryo/fetus in the maternal body and in the mother's body, changes deoxyribonucleic acid binding affinity to the myogenic factor transcription, transcriptional activity of RP11-212I21.2 gene in arteries.

CONCLUSION

The T allele rs243865 of the MMP-2 gene was found to be a risk factor for the development of FGR.