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

• Published in: The pharmacogenomics journal Vol. 12; no. 6; pp. 489 - 498
• Main Authors: Palei, A C T, Sandrim, V C, Amaral, L M, Machado, J S R, Cavalli, R C, Lacchini, R, Duarte, G, Tanus-Santos, J E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2012; Nature Publishing Group
• Subjects: 692/699/75/243/793; 692/700/565/1436/434; Adult; Alleles; Antihypertensive Agents - therapeutic use; Antihypertensive drugs; Antihypertensives; Biomedical and Life Sciences; Biomedicine; Diuretics; Dosage and administration; Drug therapy; Enzyme-linked immunosorbent assay; Female; Gelatinase B; Gene Expression; Gene polymorphism; Genetic aspects; Genetic diversity; Genetic polymorphisms; Genotype; Haplotypes; Health aspects; Human Genetics; Humans; Hypertension; Hypertension, Pregnancy-Induced - drug therapy; Hypertension, Pregnancy-Induced - enzymology; Hypertension, Pregnancy-Induced - genetics; Matrix metalloproteinase; Matrix Metalloproteinase 9 - blood; Matrix Metalloproteinase 9 - genetics; Metalloproteinase; Oncology; original-article; Patient outcomes; Pharmacotherapy; Plasma; Polymorphism; Pre-eclampsia; Pre-Eclampsia - enzymology; Pre-Eclampsia - genetics; Preeclampsia; Pregnancy; Pregnant women; Proteases; Psychopharmacology; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - blood; Brazil; gestational hypertension; polymorphism; antihypertensive therapy; preeclampsia; MMP-9; pharmacogenetics
• ISSN: 1470-269X; 1473-1150; 1473-1150
• DOI: 10.1038/tpj.2011.31

Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.−1562C>T and g.−90(CA) 13−25 ) 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.−90(CA) 13−25 polymorphism were grouped L (low) (<21 CA repeats) or H (high) (⩾21 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.−90(CA) 13−25 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.−1562C>T 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.