The journal of gene medicine 2016 8 23() doi 10.1002/jgm.2897
Astrocytes are susceptible to HIV-1 infection. The neurocognitive dysfunction has also been associated with the toxicity of certain antiretroviral drugs. The HIV-1 induced neurological toxicity has been associated with deficiency of matrix metalloproteinases. Therefore, we evaluated the association of MMP-2(-735 C > T) and MMP-9(-1562 C > T) polymorphism in susceptibility to develop HIV Associated Neurocognitive Disorders (HAND) and its severity.
We enrolled 50 HIV-infected individual with HAND, 130 without HAND and 150 unrelated healthy controls. Polymorphism for MMP-2-735 C > T and MMP-9-1562 C > T gene was genotyped by PCR-RFLP.
Individuals with MMP-2 -735CT genotype and -735T allele were at higher risk to develop HAND (OR = 5.27, 95%CI: 1.30-21.35, P = 0.02 and OR = 2.27, 95%CI: 1.57-3.27, P= 0.0001 respectively). MMP-2 -735 CT genotype and -735 T allele of MMP-2 were associated with reduced likelyhood 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). On evaluating gene-gene interaction models, the combined genotype MMP-2-735TT + MMP-9-1562CC and MMP-2-735CT + MMP-9-1562CT were associated with risk to develop HAND (OR= 4.84, P= 0.0001, OR=1.81, P=0.03). However, individuals with combined genotype of MMP-2-735TT + MMP-9-1562CC was found to be protective for severe HAND (OR=0.30, 95% CI: 0.13 – 0.67, P=0.003).
Individuals with MMP-2 -735CT genotype, -735T allele and combined genotype MMP-2 -735TT + MMP-9 -1562CC enhanced the risk to develop HAND. Whereas MMP-2 -735 CT genotype and -735 T allele and combined genotype of MMP-2-735TT + MMP-9-1562CC suggested protection from developing severe HAND.