title: Genetic variation of MMP-2(-735 C>T) and MMP-9(-1562 C>T) gene in risk of development of HAND and severity of HAND.
abstract: BACKGROUND
  Astrocytes are susceptible to HIV-1 infection. Neurocognitive dysfunction has also been associated with the toxicity of certain antiretroviral drugs. HIV-1 induced neurological toxicity has been associated with deficiency of matrix metalloproteinases. Therefore, we evaluated the association of MMP-2(-735C > T) and MMP-9(-1562C > T) polymorphisms with respect to the susceptibility of developing HIV-associated neurocognitive disorders (HAND) and its severity.
  
  
  METHODS
  We enrolled 50 HIV-infected individuals with HAND, 130 without HAND and 150 unrelated healthy controls. Polymorphism for MMP-2-735C > T and MMP-9-1562C > T genes was genotyped by polymerase chain reaction-restriction fragment length polymorphism.
  
  
  RESULTS
  Individuals with the MMP-2 -735 CT genotype and -735 T allele were at higher risk of developing HAND [odds ratio (OR) = 5.27, 95% confidence interval (CI) = 1.30-21.35, p = 0.02 and OR = 2.27, 95% CI = 1.57-3.27, p = 0.0001 respectively]. The MMP-2 -735 CT genotype and -735 T allele of MMP-2 were associated with a reduced likelihood of severe HAND (OR =0.32, 95% CI = 0.15-0.66, p = 0.002 and OR = 0.32, 95% CI = 0.14-0.71, p = 0.005). When evaluating gene-gene interaction models, the combined genotype MMP-2-735TT + MMP-9-1562CC and MMP-2-735CT + MMP-9-1562CT was associated with the risk of developing HAND (OR = 4.84, p = 0.0001, OR = 1.81, p = 0.03). However, individuals with the combined genotype of MMP-2-735TT + MMP-9-1562CC were found to be protective for severe HAND (OR = 0.30, 95% CI = 0.13-0.67, p = 0.003).
  
  
  CONCLUSIONS
  Individuals with the MMP-2 -735CT genotype, -735 T allele and combined genotype MMP-2 -735TT + MMP-9 -1562CC had an enhanced risk of developing HAND. Those with the MMP-2 -735 CT genotype, -735 T allele and combined genotype of MMP-2-735TT + MMP-9-1562CC were suggested to have protection from developing severe HAND.
authors.affiliation: Department of Molecular Biology, National AIDS Research Institute, Pune, India. hsingh@nariindia.org.
authors.forename: HariOm
authors.initials: H
authors.lastname: Singh
authors.affiliation: Department of Molecular Biology, National AIDS Research Institute, Pune, India.
authors.forename: Shruti D
authors.initials: SD
authors.lastname: Marathe
authors.affiliation: Department of Molecular Biology, National AIDS Research Institute, Pune, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Nema
authors.affiliation: Department of Clinical Sciences, National AIDS Research Institute, Pune, India.
authors.forename: Manisha V
authors.initials: MV
authors.lastname: Ghate
authors.affiliation: Department of Clinical Sciences, National AIDS Research Institute, Pune, India.
authors.forename: Raman R
authors.initials: RR
authors.lastname: Gangakhedkar
mesh_terms: D015526:AIDS Dementia Complex / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: HAND; HIV; MMP-2; MMP-9; susceptibility