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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.

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.
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Singh H, Marathe SD, Nema V, Ghate MV, Gangakhedkar RR,


Singh H, Marathe SD, Nema V, Ghate MV, Gangakhedkar RR, (click to view)

Singh H, Marathe SD, Nema V, Ghate MV, Gangakhedkar RR,

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The journal of gene medicine 2016 8 23() doi 10.1002/jgm.2897

Abstract
BACKGROUND
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.

METHODS
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.

RESULTS
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).

CONCLUSION
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.

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