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Role of MMP-13-77A/G polymorphism in HIV-associated neurocognitive disorders patients
HariOm Singh1, Kishore Dhotre1
1Department of Molecular Biology, National AIDS Research Institute Pune, 411026, India.
Abstract:
Many diseases including HIV-Associated Neurocognitive Disorder (HAND) are impacted by matrix metalloproteinases (MMPs). MMP-13 play a role to cleave the collagen. MMP-13 contributes to peripheral neuropathy and induces unmyelinated axon degeneration. MMP-13-77A/G polymorphism has been associated to a lower level of MMP-13. MMP-13 have been linked to increased expression in a number of diseases including neurological disease. Hence we analyzed the effect of MMP-13-77A/G polymorphism in pateints with and without HAND. The PCR-Restriction fragment length polymorphism approach was used to genotype MMP-13-77A/G polymorphism. The MMP-13-77AG genotype was shown to be more prevalent in HAND patients than in controls and showed a risk for severe HAND (44.4% vs. 34.8%, P = 0.16, OR = 1.79). When compared to healthy controls, the MMP-13-77AG genotype was found to be prevalent in HAND patients (44.4 %vs. 38.2%, P = 0.66, OR = 1.26). MMP-13-77AG genotype was overrepresented (51.5% vs. 38.2%, OR = 1.70, P = 0.29) in HAND patients who had advanced HIV disease. In without HAND patients, the MMP-13-77AG genotype was found be lessor in advanced stage of HIV disease when compared with healthy controls and it was associated with a reduced risk for advancement in disease (38.2% vs. 11.82%, P = 0.03, OR = 0.18). Smokers were more likely to have the MMP-13-77AG genotype than non-smokers, indicating an elevated risk of HAND severity (60.0% vs. 40.0%, P = 0.50, OR = 2.29, 95%). In patients with and without HAND, alcohol intake enhanced the risk for developing HAND and its severity when the MMP-13-77GG genotype was present (P = 0.78, OR = 2.10, P = 0.78, OR = 2.10). In conclusion, Individuals with alcohol usage and the MMP-13-77GG genotype may have additive effect on HAND development and its severity. Individuals of without HAND and MMP-13-77AG genotype showed reduced risk for advancement of HIV disease.
Insights
Matrix metalloproteinase-13 (MMP-13) gene variations impact HIV-Associated Neurocognitive Disorder (HAND). The MMP-13-77AG genotype is linked to increased HAND risk and severity, especially with alcohol consumption.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Matrix metalloproteinases (MMPs), particularly MMP-13, are implicated in various diseases, including neurological disorders.
- MMP-13 plays a role in collagen degradation and has been linked to peripheral neuropathy and axon degeneration.
- The MMP-13-77A/G polymorphism is associated with altered MMP-13 levels and has been studied in relation to neurological conditions.
Purpose of the Study:
- To investigate the association between the MMP-13-77A/G polymorphism and the risk and severity of HIV-Associated Neurocognitive Disorder (HAND).
- To explore the influence of environmental factors like smoking and alcohol consumption on the relationship between MMP-13 polymorphism and HAND.
Main Methods:
- Genotyping of the MMP-13-77A/G polymorphism using the PCR-Restriction fragment length polymorphism (PCR-RFLP) method.
- Comparison of genotype frequencies between patients with and without HAND, including subgroups based on disease severity and HIV progression.
- Analysis of the combined effects of MMP-13 genotype, smoking, and alcohol intake on HAND development and severity.
Main Results:
- The MMP-13-77AG genotype was more prevalent in HAND patients and associated with an increased risk of severe HAND.
- This genotype was overrepresented in HAND patients with advanced HIV disease.
- In individuals without HAND, the MMP-13-77AG genotype was associated with a reduced risk of HIV disease progression.
- Smoking was linked to a higher likelihood of carrying the MMP-13-77AG genotype, increasing HAND severity risk.
- Alcohol intake, particularly with the MMP-13-77GG genotype, enhanced the risk for HAND development and severity.
Conclusions:
- The MMP-13-77A/G polymorphism, specifically the -77AG genotype, is a potential risk factor for HAND development and severity.
- Environmental factors such as alcohol consumption can exacerbate the risk associated with specific MMP-13 genotypes.
- The MMP-13-77AG genotype may confer a protective effect against HIV disease progression in individuals without HAND.
