Role of MMP-1 , MMP-8 and MMP-9 gene polymorphisms in preterm birth
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Ó Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)
RESEARCH ARTICLE
Role of MMP-1, MMP-8 and MMP-9 gene polymorphisms in preterm birth MONIKA PANDEY* and SHALLY AWASTHI Department of Pediatrics, King George’s Medical University, Lucknow 226 003, India *For correspondence. E-mail: [email protected]. Received 6 January 2019; revised 17 August 2019; accepted 18 September 2019 Abstract. Novel approaches to preterm births are underway building upon our prior discoveries and probing into unknown discovery pathways. The recent findings showed a high affinity of MMP-9 in serum and its polymorphisms for preterm birth. This study, which is a hospital-based case– control study, aims to investigate the association of MMP-1, MMP-8 and MMP-9 polymorphisms, and levels of MMP-9 in preterm birth. Increased level of MMP-9 was reported in cases as compared to control. The significant association of MMP-9 (-1562) CT (P = 0.001; OR = 1.44 (CI = 0.97–2.14)) and TT genotype (P = 0.05; OR = 2.6 (CI = 1.46–4.69)) were reported in preterm birth. Our findings suggest that the MMP-9 plays an important role in contributing preterm labour and this can be used as a diagnostic tool during pregnancy. Keywords.
infection; inflammation; matrix metalloproteinases; polymorphism; preterm birth.
Introduction Preterm birth (PTB) is the most prevailing and persistent problem causing enormous morbidity and mortality among infants (Pandey et al. 2017). India itself accounts for 21% of the total global burden (Indian Foundation of Premature Babies 2014, http://www.dayofbangalore.com/news/ healthcare/indianfoundation-premature-babies-ifpb-marksworldprematurity (accessed 17 August 2018). The involvement of genetic and environmental factors are quite evident in several studies (Knight and Smith 2016; Pandey et al. 2018). However, the role of particular gene and genetic pathway are still needs to be elucidated. The causes of preterm birth and premature rupture of the membranes are associated with infection and inflammation driven pathway (Boyle et al. 2017). The maintenance of tensile strength of amniochorion is regulated by intracellular matrix metalloproteinases (MMPs) (Vadillo-Ortega and Estrada-Gutie´rrez 2005). These MMPs are zinc-dependent enzymes that takes part in the collagen processing and mainly expressed in the placenta and foetal membranes (Majali-Martinez et al. 2016). A large portion of the extracellular membrane (ECM) and parts of the cellular layer is underlined by the network of metalloproteinases (MMPs) (Bowers et al. 2010). MMP1, MMP-8, MMP-9 are the most studied candidate genes (Fanjul-Ferna´ndez et al. 2010). Their
altered gene expression may be an attributing factor of causing preterm birth (Sheikh et al. 2016). The functional polymorphisms situated in MMP-1, MMP-8 and MMP-9 promoter region may be a contributing element (Fanjul-Ferna´ndez et al. 2010). As reported by a study, an insertion deletion of single nucleotide polymorphism, i.e. single guanine (1G or 2G) situated at nucleotide 1607 in the MMP-1 promo
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