Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease
Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease
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基质金属蛋白酶9基因多态性与慢性肾脏病
DOI：
10.1159/000343742
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发表时间：
2012
期刊：
影响因子：
4.2
通讯作者：
Wakai K; Japan Multi-Institutional Collaborative Cohort (J-MICC) Study Group
中科院分区：
文献类型：
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作者：
Okada R;Kawai S;Naito M;Hishida A;Hamajima N;Shinchi K;Chowdhury Turin T;Suzuki S;Mantjoro EM;Toyomura K;Arisawa K;Kuriyama N;Hosono S;Mikami H;Kubo M;Tanaka H;Wakai K; Japan Multi-Institutional Collaborative Cohort (J-MICC) Study Group
背景：本研究的目的是探讨慢性肾脏病（CKD）患病率与编码基质金属蛋白酶（MMPs）和基质金属蛋白酶组织抑制剂（TIMP）的基因多态性之间的关系。MMPs降解肾小球细胞外基质蛋白，在肾脏疾病的进展中发挥重要作用。方法：对3,309例年龄在35-69岁的受试者的DNA样本进行MMP和TIMP基因10个潜在的功能多态性基因分型。结果：随着MMP 9 C-1562 T（CT与CC相比，OR值分别为0.77和0.65;趋势p = 0.023）和MMP 9 R668 Q（RQ与RR相比，OR值分别为0.79和0.64;趋势p = 0.024）次要等位基因数量的增加，CKD患病率显著降低。单体型MMP 9 - 1562 T/279 R/668 Q与最常见的-1562 C/279 R/668 R相比，显示CKD风险降低（OR 0.77，p = 0.008），基因型组合-1562 TT/279 RR/668 QQ与主要等位基因纯合子-1562 CC/279 RR/668 RR相比，显示CKD风险减半结论：MMP 9基因的功能多态性与日本人群中CKD的患病率相关。据报道，这些基因型可增加MMP-9的表达，支持MMP-9在肾脏疾病进展中具有保护作用的假设。
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 inMMPandTIMPgenes. 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 inMMP9C–1562T (odds ratios (ORs) 0.77 for CT and 0.65 for TT compared with CC; p for trend = 0.023) andMMP9R668Q (ORs, 0.79 for RQ and 0.64 for QQ compared with RR; p for trend = 0.024). The haplotypeMMP9–1562T/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 ofMMP9were associated with the prevalence of CKD in a large Japanese population. These genotypes have been reported to increaseMMP9expression, supporting the hypothesis that MMP-9 has a protective role in the progression of kidney diseases.