Genetic variation in the matrix metalloproteinase genes and diabetic nephropathy in type 1 diabetes.
Genetic variation in the matrix metalloproteinase genes and diabetic nephropathy in type 1 diabetes.
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DOI：
10.1016/j.ymgme.2011.01.001
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发表时间：
2011-05
影响因子：
3.8
通讯作者：
Krolewski, Andrzej S.
中科院分区：
文献类型：
--
作者：
Kure, Masahiko;Pezzolesi, Marcus G.;Poznik, G. David;Katavetin, Pisut;Skupien, Jan;Dunn, Jonathon S.;Mychaleckyj, Josyf C.;Warram, James H.;Krolewski, Andrzej S.
关键词：
遗传学数据支持这样的观点，即基质金属蛋白酶（MMP）基因家族成员的多态性在细胞外基质重塑中起重要作用，并有助于血管疾病的发病机制。为了鉴定糖尿病肾病（DN）的新遗传标记，我们在糖尿病肾脏遗传学（GoKinD）人群中研究了MMP基因多态性与DN之间的关系。分析了来自遗传关联信息网络（GAIN）1型DN项目的基因型数据，以确定1，705名1型糖尿病患者（包括885名正常白蛋白尿对照受试者和820名晚期DN病例受试者）中21个MMP基因之间的关联。总之，我们研究了1,283个SNP（198个基因型SNP和1,085个估算的SNP）定位到MMP基因的作用。我们确定了MMP-3/MMP-12基因座上染色体11 q上29.2 kb间隔内几个相关SNP的相关性。最强的关联发生在两个高度相关的SNP，rs610950（OR = 0.50，P = 1.6×10 - 5）和rs 1277718（OR = 0.50，P = 2.1×10 - 5）。对该基因座的进一步检查确定了17个SNP（2个基因型SNP和15个插补SNP）与DN相关的完全连锁不平衡（P值< 2.5×10−4），包括非同义SNP（rs652438，Asn 357 Ser），与天冬酰胺纯合子携带者相比，丝氨酸替换携带者发生DN的风险显著降低（OR = 0.51; 95%CI = 0.37-0.71，P = 6.2×10−5）。综上所述，我们的研究表明，MMP-3/MMP-12基因座内的遗传变异影响1型糖尿病DN的易感性。
Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type 1 DN project were analyzed for associations across 21 MMP genes in 1,705 individual with type 1 diabetes, including 885 normoalbuminuric control subjects and 820 advanced DN case subjects. In total, we investigated the role of 1,283 SNPs (198 genotyped SNPs and 1,085 imputed SNPs) mapping to the MMP genes. We identified associations at several correlated SNPs across a 29.2 kb interval on chromosome 11q at the MMP-3/MMP-12 locus. The strongest associations occurred at 2 highly-correlated SNPs, rs610950 (OR = 0.50, P = 1.6×10−5) and rs1277718 (OR = 0.50, P = 2.1×10−5). Further examination of this locus identified 17 SNPs (2 genotyped SNPs and 15 imputed SNPs) in complete linkage disequilibrium associated with DN (P-values < 2.5×10−4), including a non-synonymous SNP (rs652438, Asn357Ser) located in exon 8 of MMP-12 that significantly reduced the risk of DN among carriers of the serine substitution relative to homozygous carriers of asparagine (OR = 0.51; 95% CI = 0.37–0.71, P = 6.2×10−5). Taken together, our study suggests that genetic variations within the MMP-3/MMP-12 locus influence susceptibility of DN in type 1 diabetes.
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影响因子：
4.2
作者：
Ishizaki, E;Takai, S;Miyazaki, M
通讯作者：
Miyazaki, M
对糖尿病性肾病中纤维化和硬化症机制的新见解。
影响因子：
8.2
作者：
Brosius, Frank C., III
通讯作者：
Brosius, Frank C., III
影响因子：
6.1
作者：
Kosano, H;Okano, T;Nishigori, H
通讯作者：
Nishigori, H
影响因子：
3.7
作者：
Thrailkill, Kathryn M.;Bunn, R. Clay;Fowlkes, John L.
通讯作者：
Fowlkes, John L.
影响因子：
3.3
作者：
Pezzolesi, Marcus G.;Skupien, Jan;Mychaleckyj, Josyf C.;Warram, James H.;Krolewski, Andrzej S.
通讯作者：
Krolewski, Andrzej S.