Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease

Rieko Okada, Sayo Kawai, Mariko Naito, Asahi Hishida, Nobuyuki Hamajima, Koichi Shinchi, Tanvir Chowdhury Turin, Sadao Suzuki, Eva Mariane Mantjoro, Kengo Toyomura, Kokichi Arisawa, Nagato Kuriyama, Satoyo Hosono, Haruo Mikami, Michiaki Kubo, Hideo Tanaka, Kenji Wakai

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Abstract

Background: The aim of this study was to explore the associations between the prevalence of chronic kidney disease (CKD) and polymorphisms in the genes encoding matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs). MMPs degrade extracellular matrix proteins in the glomerulus, and play important roles in kidney disease progression. Methods: DNA samples from 3,309 subjects aged 35-69 years were genotyped for 10 potentially functional polymorphisms in MMP and TIMP genes. The prevalence of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2) was compared among the genotypes. Results: The prevalence of CKD decreased significantly with the number of minor alleles in MMP9 C-1562T (odds ratios (ORs) 0.77 for CT and 0.65 for TT compared with CC; p for trend = 0.023) and MMP9 R668Q (ORs, 0.79 for RQ and 0.64 for QQ compared with RR; p for trend = 0.024). The haplotype MMP9-1562T/279R/668Q showed a reduced risk for CKD compared with the most common-1562C/279R/668R (OR 0.77, p = 0.008), and the genotype combination-1562TT/279RR/668QQ showed a halved risk for CKD compared with major allele homozygous-1562CC/279RR/668RR (OR 0.53, p = 0.091). Conclusion: The potentially functional polymorphisms of MMP9 were associated with the prevalence of CKD in a large Japanese population. These genotypes have been reported to increase MMP9 expression, supporting the hypothesis that MMP-9 has a protective role in the progression of kidney diseases.

Original languageEnglish
Pages (from-to)444-450
Number of pages7
JournalAmerican Journal of Nephrology
Volume36
Issue number5
DOIs
Publication statusPublished - 01-11-2012

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All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Okada, R., Kawai, S., Naito, M., Hishida, A., Hamajima, N., Shinchi, K., Chowdhury Turin, T., Suzuki, S., Mantjoro, E. M., Toyomura, K., Arisawa, K., Kuriyama, N., Hosono, S., Mikami, H., Kubo, M., Tanaka, H., & Wakai, K. (2012). Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease. American Journal of Nephrology, 36(5), 444-450. https://doi.org/10.1159/000343742