Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

Abstract

Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.À1562C4T and g.À90(CA) 13À25 ) modify plasma MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels and the responses to antihypertensive therapy in 214 patients with preeclampsia (PE), 185 patients with gestational hypertension (GH) and a control group of 214 healthy pregnant (HP). Alleles for the g.À90(CA) 13À25 polymorphism were grouped L (low) (o21 CA repeats) or H (high) (X21 CA repeats). Plasma MMP-9 and TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay. Plasma MMP-9 concentrations were not affected by genotypes or haplotypes in HP and PE groups, except for the g.À90(CA) 13À25 polymorphism: GH patients with the LH genotype for this polymorphism have higher MMP-9 levels than those with other genotypes. The T allele for the g.À1562C4T polymorphism and the H4 haplotype (combining T and H alleles) are associated with GH and lack of responsiveness to antihypertensive therapy in GH. The H2 haplotype (combining C and H alleles) was associated with lack of responsiveness to antihypertensive therapy in PE, but not in GH. In conclusion, our results show that MMP-9 genetic variants are associated with GH and suggest that MMP-9 haplotypes affect the responsiveness to antihypertensive therapy in hypertensive disorders of pregnancy.

Is there any genetic predisposition of MMP-9 gene C1562T and MTHFR gene C677T polymorphisms with essential hypertension?

“…On the contrary to the results of the current study, they reported that C1562T polymorphism may correlate with gestational hypertension. Nevertheless, another study reported that T allele for the C1562T polymorphism is associated with gestational hypertension (Palei et al 2012). In a study conducted by Lacchini et al (2010) the authors determined that the frequency of 1562 CC genotype, CT genotype and TT genotype was 75, 25 and 0 %, respectively, in hypertensive patients, while corresponding frequencies were 80, 18 and 2 % in control subjects.…”

Investigation of the association between matrix metalloproteinase-9 genetic polymorphisms and development of pre-eclampsia in Chinese pregnant women

“…Additionally, several studies have reported an association between MMP-9 genetic polymorphism and the development of pre-eclampsia; however, the results of these studies are inconclusive (Coolman et al, 2007;Fraser et al, 2008;Palei et al, 2010Palei et al, , 2012Luizon et al, 2012;Rahimi et al, 2013Rahimi et al, , 2014Rahimi et al, , 2015. Some studies suggested that the CC genotype or C allele of MMP-9 -1562 C/T is associated with increased risk of developing pre-eclampsia in Caucasian pregnant women (Coolman et al, 2007;Luizon et al, 2012;Rahimi et al, 2013Rahimi et al, , 2014Rahimi et al, , 2015.…”

Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy

“…We reported associations of some genotypes and haplotypes formed by these polymorphisms with PE and/or gestational hypertension (GH). [18][19][20][21] These studies indicate that, at least individually, these genes may be important to the development of these disorders. Besides the study of these genes independently, epistasis has also been suggested to be an important component of complex diseases, including PE.…”

“…Seven clinically relevant polymorphisms were studied in eNOS (T-786C, rs2070744 in the promoter region; the 27 bp variable number of tandem repeats in intron 4; and Glu298Asp, rs1799983 in exon 7), in the promoter region of MMP-9 (C-1562T, rs3918242 and -90(CA) [13][14][15][16][17][18][19][20][21][22][23][24][25] , rs2234681), and in the promoter region of VEGF (C-2578A, rs699947 and G-634C, rs2010963). Genotypes for eNOS rs2070744 and rs1799983 and for VEGF polymorphisms were determined by TaqMan allele discrimination assays using probes and primers designed by Applied Biosystems (Carlsbad, CA, USA), as previously described.…”

“…They have largely focused on maternal genotypes, and polymorphisms in genes involved in angiogenesis, endothelial function and oxidative stress have been associated with PE. [15][16][17] We previously studied clinically relevant polymorphisms of the eNOS (T-786C, 27 bp variable number of tandem repeats in intron 4 and Glu298Asp), MMP-9 (C-1562T and -90(CA) [13][14][15][16][17][18][19][20][21][22][23][24][25] ) and VEGF (C-2578A and G-634C) genes in HDP. We reported associations of some genotypes and haplotypes formed by these polymorphisms with PE and/or gestational hypertension (GH).…”