Matrix Metalloproteinase-9 Gene Polymorphisms and Chronic Kidney Disease

被引:17
作者
Okada, Rieko [1 ]
Kawai, Sayo
Naito, Mariko
Hishida, Asahi
Hamajima, Nobuyuki
Shinchi, Koichi [2 ]
Turin, Tanvir Chowdhury [3 ,4 ]
Suzuki, Sadao [5 ]
Mantjoro, Eva Mariane [6 ]
Toyomura, Kengo [7 ]
Arisawa, Kokichi [8 ]
Kuriyama, Nagato [9 ]
Hosono, Satoyo [10 ]
Mikami, Haruo [11 ]
Kubo, Michiaki [12 ]
Tanaka, Hideo [10 ]
Wakai, Kenji
机构
[1] Nagoya Univ, Grad Sch Med, Dept Prevent Med, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Saga Univ, Fac Med, Dept Community & Int Hlth Nursing, Saga 840, Japan
[3] Shiga Univ Med Sci, Dept Hlth Sci, Otsu, Shiga 52021, Japan
[4] Univ Calgary, Dept Med, Calgary, AB, Canada
[5] Nagoya City Univ, Grad Sch Med Sci, Dept Publ Hlth, Nagoya, Aichi, Japan
[6] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Int Isl & Community Med, Kagoshima 890, Japan
[7] Kyushu Univ, Grad Sch Med Sci, Dept Prevent Med, Fukuoka 812, Japan
[8] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Prevent Med, Tokushima 770, Japan
[9] Kyoto Prefectural Univ Med, Dept Epidemiol Community Hlth & Med, Kyoto, Japan
[10] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan
[11] Chiba Canc Ctr, Div Canc Registry Prevent & Epidemiol, Chiba 2608717, Japan
[12] RIKEN, Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa, Japan
关键词
Chronic kidney disease; Matrix metalloproteinase; Polymorphism; Renal insufficiency; MULTIINSTITUTIONAL COLLABORATIVE COHORT; MATRIX METALLOPROTEINASES; HEMODIALYSIS-PATIENTS; MMP9; GENE; ASSOCIATION; EXPRESSION; ACTIVATION; VARIANTS;
D O I
10.1159/000343742
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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 m(2)) 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. Copyright (C) 2012 S. Karger AG, Basel
引用
收藏
页码:444 / 450
页数:7
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