Journal of Biosciences

, Volume 42, Issue 3, pp 481–490 | Cite as

Promoter polymorphism MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) in development of HAND and modulation of pathogenesis of HAND

  • Hari Om Singh
  • Shruti D Marathe
  • Sumitra Nain
  • Dharmesh Samani
  • Vijay Nema
  • Manisha V Ghate
  • R R Gangakhedkar
Article
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Accepted:

Abstract

The pathogenesis of HIV-associated neurocognitive disorder (HAND) is modulated by host genetic susceptibility factors such as Matrix metalloproteinases (MMPs). Promoter polymorphism of MMP-1 and MMP-3 may modify the expression of the gene. Hence, we evaluated the association of MMP-1-16072G/1G and MMP-3-1612 5A/6A polymorphisms with development of HAND and the modulation of pathogenesis of HAND. We enrolled a total of 180 individuals, 50 HIV-infected individuals with HAND, 130 without HAND, and 150 healthy controls. Polymorphism of MMP-1 and MMP-3 were genotyped by PCR-RFLP. MMP-1-1607 2G1G, -16071G/2G-1G/1G genotypes and -1607 1G allele were associated with the development of HAND (OR = 1.64, P = 0.05; OR = 1.45, P = 0.04; OR = 1.69, P = 0.05). MMP-1-16071G1G, MMP-3-16125A5A genotypes increased the risk for the development of HAND (OR = 1.78, P = 0.25; OR = 2.39, P = 0.13). MMP-3-1612 5A5A, -1612 6A/5A-5A/5A genotypes and -1612 5A allele were associated with the reduced risk of HAND (OR = 0.40, P = 0.05; OR = 0.53, P = 0.04; OR = 0.40, P = 0.01). Haplotype 5A1G increased the risk of development of HAND (OR = 1.93, P = 0.05). As observed in advanced HIV disease stage, MMP-1-1607 1G1G genotype enhance the risk for advancement of HIV disease (OR = 1.69, P = 0.89). MMP-3-1612 6A5A genotype showed higher risk for development of HAND in alcohol users (0R = 1.65, P = 0.44). MMP-1 genotype may have an influence on development of HAND whereas MMP3-1612 5A5A genotype may reduce risk for pathogenesis of HAND.

Keywords

Development of HAND genetic susceptibility HAND MMP-1 MMP-3 
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Notes

Acknowledgements

We gratefully acknowledge Seema Sahay, in charge of the clinic, for the arrangement of community staff for recruitment of healthy control; Mansa Angadi, Shradha Bapat and Jyoti Pawar for filling the clinical research proforma; Tumnan Katendra, Jai and Iyesha for counselling of subject participants; and sisters Ujawala Ghule and Sunita for the collection of blood samples. The study was supported by a research grant provided by NARI- ICMR India. The study was supported by research grant from Indian Council of Medical Research (ICMR) India (grant number HIV/50/152/10/2012-ECD-II).

Supplementary material

12038_2017_9694_MOESM1_ESM.docx (768 kb)
Supplementary material 1 (DOCX 767 kb)

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Copyright information

© Indian Academy of Sciences 2017

Authors and Affiliations

  • Hari Om Singh
    • 1
  • Shruti D Marathe
    • 1
  • Sumitra Nain
    • 1
  • Dharmesh Samani
    • 1
  • Vijay Nema
    • 1
  • Manisha V Ghate
    • 2
  • R R Gangakhedkar
    • 2
  1. 1.Department of Molecular BiologyNational AIDS Research InstitutePuneIndia
  2. 2.Department of Clinical SciencesNational AIDS Research InstitutePuneIndia

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