A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients

Abstract

We examined whether two functional polymorphisms (g.À1562C4T and g.À90(CA)14-24) in the matrix metalloproteinase (MMP)-9 gene or MMP-9 haplotypes affect the circulating levels of pro-MMP-9 and pro-MMP-9/TIMP-1 (tissue inhibitor of metalloproteinase-1) ratios in AIDS patients, and modulate alterations in these biomarkers after highly active antiretroviral therapy (HAART). We studied 82 patients commencing HAART. Higher pro-MMP-9 concentrations and pro-MMP-9/TIMP-1 ratios were found in CT/TT patients compared with CC patients. HAART decreased pro-MMP-9 levels and pro-MMP-9/TIMP-1 ratios in CT/TT patients, it did not modify pro-MMP-9 levels and it increased pro-MMP-9/TIMP-1 ratios in CC patients. The g.À90(CA)14-24 polymorphism, however, produced no significant effects. Moreover, we found no significant differences in HAARTinduced changes in plasma pro-MMP-9, TIMP-1 and pro-MMP-9/TIMP-1 ratios when different MMP-9 haplotypes were compared. These findings suggest that the g.À1562C4T polymorphism affects pro-MMP-9 levels in patients with AIDS and modulates the alterations in pro-MMP-9 levels caused by HAART, thus possibly affecting the risk of cardiovascular complications.

Genetic Variants in Matrix Metalloproteinase-9 Gene Modify Metalloproteinase-9 Levels in Black Subjects

“…Therefore, it is reasonable to suspect that genetic polymorphisms in the genes encoding MMPs may affect their circulating levels and predispose to cardiovascular diseases. Indeed, this suggestion has been confirmed in previous studies showing that genetic polymorphisms in the MMP-9 gene affect the circulating levels of MMP-9 in patients, as well as the prognosis (Blankenberg et al, 2003;Demacq et al, 2009).…”

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

“…17 However, the (CA) 14 allele causes a 50% reduction in MMP-9 promoter activity as compared with the (CA) 21 . 18,19 Interestingly, these polymorphisms may affect drug responses 20 and both polymorphisms have been associated with PE or GH, 21,22 thus suggesting that MMP-9 genetic variations may predispose to hypertensive disorders of pregnancy. However, no previous study has examined whether MMP-9 polymorphisms affect MMP-9 levels in hypertensive disorders of pregnancy and whether MMP-9 polymorphisms modify the antihypertensive responses in these conditions.…”

Specific matrix metalloproteinase 9 (MMP-9) haplotype affect the circulating MMP-9 levels in women with migraine

“…Differences in molecular weight (or number of bases), from 146 bp (CA 14 repeats) to 166 bp (CA 24 repeats) were determined by comparison with migration of a 10 bp DNA ladder (Invitrogen, Carlsbad, CA, USA) and with some samples from homozygotes that were sequenced. The alleles for the microsatellite −90(CA) 14-24 polymorphism were classified as "low" (L) count when the number of CA repeats was less than 21, and as "high" (H) when the number of CA repeats was 21 or more (Demacq et al, 2009).…”

“…Mounting evidence suggests that MMP-9 gene polymorphisms may affect MMP-9 levels, the progression of disease conditions and therapeutic responses (Demacq et al, 2009;Jacob-Ferreira et al, 2010b;Lacchini et al, 2010;Belo et al, 2012;Palei et al, in press). Relevant functional MMP-9 polymorphisms include the C(−1562)T polymorphism (Zhang et al, 1999), a microsatellite −90(CA) n (13-25 repeats) in promoter region (Shimajiri et al, 1999), and the Q279R in exon 6 (Allan et al, 1995).…”