Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder
The imbalance between MMPs and TIMPs is associated with the HIV dissemination tissue damage pathology neurodegenerative disorders, including HAND. Genetic variations in the TIMP gene may modulate the neurocognitive disorder in HIV patients. Hence, we evaluated the genetic variants of TIMP-2 (-418G/C...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/8278095 |
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| author | HariOm Singh Sushma Jadhav Dharmesh Samani Sumitra Nain |
| author_facet | HariOm Singh Sushma Jadhav Dharmesh Samani Sumitra Nain |
| author_sort | HariOm Singh |
| collection | DOAJ |
| description | The imbalance between MMPs and TIMPs is associated with the HIV dissemination tissue damage pathology neurodegenerative disorders, including HAND. Genetic variations in the TIMP gene may modulate the neurocognitive disorder in HIV patients. Hence, we evaluated the genetic variants of TIMP-2 (-418G/C, 303G/A) gene with the risk of HAND. Genotyping of TIMP-2 polymorphism was performed in 50 patients with HAND, 100 no HAND, and 154 healthy controls by PCR-RFLP. TIMP-2 -418GC and 303AA genotypes represented a predominant risk for HAND severity (OR=1.55, P=0.30; OR=4.58, P=0.24). The variant -418CC genotype, -418A allele, had exhibited a significant risk for the acquisition of HAND (OR=12.55, P=0.026; OR=2.66, P=0.004). TIMP-2 303GA, 303AA genotype, and 303A allele evinced a higher risk for HAND severity (OR=1.82, P=0.14; OR=1.70, P=0.63; and OR=1.68, P=0.12). In HIV patients, TIMP-2 -418CC genotype and -418C allele significantly occurred in comparison to healthy controls (OR=10.10, P=0.006; OR=2.02, P=0.009). In the intermediate and early HIV disease stage, TIMP-2 -418CC genotype was significantly increased compared with healthy controls (11.1% vs. 1.3%, OR=14.63, P=0.01; 16.9% vs. 1.3%, OR=14.51, P=0.002). In patients with HAND among tobacco and alcohol users, TIMP-2 -418CC genotype displayed a risk for HAND severity (OR=3.96, P=0.26; OR=4.83, P=0.19). On multivariate logistic regression, TIMP-2 303AA genotype, advanced stage, and gender had a risk for HAND severity (OR=28.98, P=0.02; OR=2.35, P=0.070; and OR=2.36, P=0.04). In conclusion, TIMP-2 -418G/C polymorphism independently, along with alcohol and tobacco, may have an impact on the acquisition of HAND and its severity. TIMP-2 303G/A polymorphism bare a risk for HAND severity. |
| format | Article |
| id | doaj-art-da0ed285283345b09dd2009d291d0fd0 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
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| series | Mediators of Inflammation |
| spelling | doaj-art-da0ed285283345b09dd2009d291d0fd02025-02-03T05:43:56ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/82780958278095Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive DisorderHariOm Singh0Sushma Jadhav1Dharmesh Samani2Sumitra Nain3Department of Molecular Biology, National AIDS Research Institute, Pune 411026, IndiaDepartment of Molecular Biology, National AIDS Research Institute, Pune 411026, IndiaDepartment of Molecular Biology, National AIDS Research Institute, Pune 411026, IndiaDepartment of Pharmacy, University of Banasthali, Banasthali Vidyapith, Jaipur 302001, IndiaThe imbalance between MMPs and TIMPs is associated with the HIV dissemination tissue damage pathology neurodegenerative disorders, including HAND. Genetic variations in the TIMP gene may modulate the neurocognitive disorder in HIV patients. Hence, we evaluated the genetic variants of TIMP-2 (-418G/C, 303G/A) gene with the risk of HAND. Genotyping of TIMP-2 polymorphism was performed in 50 patients with HAND, 100 no HAND, and 154 healthy controls by PCR-RFLP. TIMP-2 -418GC and 303AA genotypes represented a predominant risk for HAND severity (OR=1.55, P=0.30; OR=4.58, P=0.24). The variant -418CC genotype, -418A allele, had exhibited a significant risk for the acquisition of HAND (OR=12.55, P=0.026; OR=2.66, P=0.004). TIMP-2 303GA, 303AA genotype, and 303A allele evinced a higher risk for HAND severity (OR=1.82, P=0.14; OR=1.70, P=0.63; and OR=1.68, P=0.12). In HIV patients, TIMP-2 -418CC genotype and -418C allele significantly occurred in comparison to healthy controls (OR=10.10, P=0.006; OR=2.02, P=0.009). In the intermediate and early HIV disease stage, TIMP-2 -418CC genotype was significantly increased compared with healthy controls (11.1% vs. 1.3%, OR=14.63, P=0.01; 16.9% vs. 1.3%, OR=14.51, P=0.002). In patients with HAND among tobacco and alcohol users, TIMP-2 -418CC genotype displayed a risk for HAND severity (OR=3.96, P=0.26; OR=4.83, P=0.19). On multivariate logistic regression, TIMP-2 303AA genotype, advanced stage, and gender had a risk for HAND severity (OR=28.98, P=0.02; OR=2.35, P=0.070; and OR=2.36, P=0.04). In conclusion, TIMP-2 -418G/C polymorphism independently, along with alcohol and tobacco, may have an impact on the acquisition of HAND and its severity. TIMP-2 303G/A polymorphism bare a risk for HAND severity.http://dx.doi.org/10.1155/2019/8278095 |
| spellingShingle | HariOm Singh Sushma Jadhav Dharmesh Samani Sumitra Nain Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder Mediators of Inflammation |
| title | Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder |
| title_full | Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder |
| title_fullStr | Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder |
| title_full_unstemmed | Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder |
| title_short | Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder |
| title_sort | tissue inhibitor of metalloproteinase 2 polymorphisms and risk for hiv associated neurocognitive disorder |
| url | http://dx.doi.org/10.1155/2019/8278095 |
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