title: Impact of variants of MMP-7(-181A>G) gene in susceptibility to the development of HIV-associated neurocognitive disorder and its severity.
abstract: The HIV-1-induced neurological toxicity has been associated with the deficiency of matrix metalloproteinases. Tat protein of HIV up regulates MMP-7 release and activation, leading to neurotoxicity. The SNP -181A>G of MMP-7 is known to have functional effects on its promoter activity. Therefore, we aimed to evaluate the association of variants of MMP-7 -181A>G gene in HIV-associated neurocognitive disorder (HAND). In the present case-control study, we recruited 50 HIV-infected individuals with HAND, 130 HIV-infected individuals without HAND and 150 unrelated healthy individuals. Polymorphism for MMP-7 -181A>G gene was genotyped by PCR-RFLP method. Frequency of -181GG and G allele of MMP-7 did not differ significantly between patients with HAND and without HAND (8.0% vs 13.1%, p = 0.22 and 31% vs 38.1%, p = 0.21). Individuals with -181 AG, -181GG genotype, and G allele of MMP-7 were found to have reduced the risk of development of HAND but not significant (50.0% vs 51.9%, p = 0.09, OR = 0.54; 13.1% vs 19.0%, p = 0.33, OR = 0.71 and 38.1% vs 44.9%, p = 0.09, OR = 0.75). Individuals in early HIV disease stage having -181AG genotype and -181AG + GG combined genotype of MMP-7 were not associated with the development of HAND (OR = 1.27, p = 0.25 and OR = 1.25, p = 0.17). Tobacco and alcohol consumption among individuals with any genotype of MMP-7 was not associated with the risk of development of HAND. In conclusion, individuals with -181GG genotype and G allele had no impact on susceptibility to the development of HAND and its severity.
authors.affiliation: Department of Molecular Biology, National AIDS Research Institute, Pune, India. hsingh@nariindia.org, hariomsgpgims@gmail.com.
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 Pharmacy, Banasthali University, Rajasthan, India.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Nain
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: Mansa
authors.initials: M
authors.lastname: Angadi
authors.affiliation: Department of Clinical Sciences, National AIDS Research Institute, Pune, India.
authors.forename: Shradha S
authors.initials: SS
authors.lastname: Bapat
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; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: HIV; HIV-associated neurocognitive disorder; MMP-7; development of HIV-associated neurocognitive disorder; genetic susceptibility