Genetic variants in matrix metalloproteinase-9 gene modify metalloproteinase-9 levels in black subjects

DNA Cell Biol. 2012 Apr;31(4):504-10. doi: 10.1089/dna.2011.1388. Epub 2011 Sep 21.

Abstract

Altered matrix metalloproteinases (MMPs) levels are involved in cardiovascular diseases and increased MMP-9 levels enhance the cardiovascular risk in apparently healthy subjects. We investigated the effects of MMP-9 gene polymorphisms and haplotypes on the circulating MMP-9 levels in healthy black subjects and the effects of an MMP-2 polymorphism on the plasma MMP-2 concentrations. We studied 190 healthy subjects, nonsmokers, self-reported as blacks (18-63 years). Genotypes for the MMP-2 C(-1306)T polymorphism and the MMP-9 C(-1562)T, 90(CA)(14-24) and Q279R polymorphisms (rs243865, rs3918242, rs2234681, and rs17576, respectively) were determined by TaqMan(®) Allele Discrimination assay and real-time polymerase chain reaction or restriction fragment length polymorphism. Alleles for the 90(CA)(14-24) polymorphism were grouped as low (L) when there were <21 and high (H) when there were ≥21 CA repeats. The plasma levels of MMP-2 and MMP-9 were determined by gelatin zymography. The software PHASE 2.1 was used to estimate the haplotypes frequencies. Although we found no effects of the MMP-9 C(-1562)T or the Q279R polymorphisms on MMP-9 levels, higher MMP-9 levels were associated with the HH genotype for the -90(CA)(14-24) polymorphism compared with the HL or LL genotypes. Lower MMP-9 levels were found in carriers of the CRL haplotype (combining the C, R, and L alleles for the MMP-9 polymorphisms) compared with the CRH haplotype. Consistent with this finding, the CRL haplotype was more commonly found in subjects with low MMP-9 levels. The MMP-2 C(-1306)T polymorphism had no effects on the plasma MMP-2 levels. Our results show that MMP-9 genetic variations modify MMP-9 levels in black subjects and may offer biochemical evidence implicating MMP-9 in the pathogenesis of cardiovascular diseases in blacks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Black People / genetics*
  • Brazil
  • DNA Primers / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Genetic Variation*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Matrix Metalloproteinase 9 / blood*
  • Matrix Metalloproteinase 9 / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics

Substances

  • DNA Primers
  • Matrix Metalloproteinase 9