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MMP-1 and -3 haplotype is associated with congenital anomalies of the kidney and urinary tract

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Abstract

Background

Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of progressive chronic kidney disease that may lead to end-stage renal disease and renal replacement therapy in childhood. Altered expression or activity of matrix metalloproteinases (MMPs) have been found in CAKUT. The MMP-1, -3, and -8 polymorphisms studied here are located in the gene promoters and alter expression. Our aim was to investigate associations of MMP polymorphisms, solely and in haplotypes, with CAKUT in children.

Methods

A case–control study with 101 pediatric patients and 281 controls was performed. The MMP-1 (-1607 1G/2G), -3 (5A/6A), and -8 (-799 C/T) genotypes were determined by PCR–restriction fragment length polymorphism.

Results

We found statistically significant associations of MMP-3 5A/6A polymorphism (p < 0.0001) and 1G−1607-6A haplotype, with no preferences for MMP-8 -799C or T alleles, with CAKUT (OR = 2.93, 95 % CI 1.43–5.98, adjusted for gender, p = 0.003) and with obstructive uropathies in a subgroup of patients (OR = 4.57, 95 % CI 2.74–7.61, adjusted for gender, p < 0.0001).

Conclusions

MMP-3 genotypes and MMP-3 and -1 haplotypes encompassing either MMP-8 -799C or T alleles were associated with CAKUT and obstructive uropathies in pediatric patients. Still, functional and association studies are needed to elucidate evident roles of MMPs in CAKUT.

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Acknowledgments

This work was supported by Serbian Government Research Grant OI175085.

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Authors and Affiliations

  1. Institute of Nuclear Sciences Vinca, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia

    Tamara Djuric, Maja Zivkovic, Magdalena Andjelevski & Aleksandra Stankovic

  2. Department of Nephrology, Institute of Children and Youth Health care, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

    Biljana Milosevic

  3. Department of Nephrology, University Children’s Hospital, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Mirjana Cvetkovic & Mirjana Kostic

  4. Institute of Nuclear Sciences Vinca, Laboratory for Radiobiology and Molecular Genetics, PO Box 522, Belgrade, Serbia

    Aleksandra Stankovic

Authors
  1. Tamara Djuric
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  2. Maja Zivkovic
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  3. Biljana Milosevic
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  4. Magdalena Andjelevski
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  5. Mirjana Cvetkovic
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  6. Mirjana Kostic
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  7. Aleksandra Stankovic
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Correspondence to Aleksandra Stankovic.

Additional information

Tamara Djuric and Maja Zivkovic contributed equally to this work.

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Djuric, T., Zivkovic, M., Milosevic, B. et al. MMP-1 and -3 haplotype is associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 29, 879–884 (2014). https://doi.org/10.1007/s00467-013-2699-x

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  • DOI: https://doi.org/10.1007/s00467-013-2699-x

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