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Effect of matrix metalloproteinase‐21 (572C/T) polymorphism on HIV‐associated neurocognitive disorder
Authors:HariOm Singh  Dharmesh Samani  Nayana Nambiar  Manisha V Ghate  R R Gangakhedkar
Institution:1. Department of Molecular Biology, National AIDS Research Institute, Pune, India;2. Department of Clinical Sciences, National AIDS Research Institute, Pune, India
Abstract:Remodeling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is a presumed reason for the development of HIV‐associated neurocognitive disorders (HAND). The coding region polymorphism in MMP‐21 572C/T gene may have a potential functional effect on ECM remodeling. Hence, we aimed to examine the association of MMP‐21 polymorphism with the modulation of HAND severity and its prevalence in HIV‐infected and healthy individuals. Genotyping of MMP‐21 572C/T polymorphism was performed by PCR‐RFLP in total 150 HIV‐infected individuals, 50 with HAND, 100 without HAND and 150 healthy controls. MMP‐21 572TT genotype was predominantly higher in HAND patients compared with no HAND (OR = 1.63, p = 0.57). MMP‐21 572T allele was associated with reduce risk for HAND severity (OR = 0.50, p = 0.04). Similarly, MMP‐21 572TT genotype underrepresented in HIV‐infected individuals compared to healthy controls (3.0% vs 6.7%, OR = 0.27, p = 0.08). MMP‐21 572CT genotype and early HIV disease stage showed a higher risk for the advancement of HIV disease with marginal significance (OR = 1.89, p = 0.07). MMP‐21 572CT genotype increased the risk for the modulation of HAND severity in tobacco users (OR = 1.98, p = 0.43). MMP‐21 572CT genotype among tobacco and alcohol users showed elevated risk for the development of HAND in HIV‐infected individuals (OR = 2.30, p = 0.15; OR = 1.86, p = 0.23). Similarly, MMP‐21 572TT genotype enhanced the risk for the development of HAND in tobacco users (OR = 3.48, p = 0.40). In conclusion, the presence of coding region 572T allele may have protection for HAND severity. MMP‐21 572C/T polymorphism and tobacco and alcohol usage may facilitate the development of HAND.
Keywords:Genetic predisposition  matrix metalloproteinase  HIV‐associated neurocognitive disorders  HIV‐infected individuals  association studies
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