Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy.
Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy.
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DOI：
10.1186/1471-2369-14-126
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发表时间：
2013-06-18
期刊：
影响因子：
2.3
通讯作者：
Warren 3/UK GoKinD Study Group
中科院分区：
文献类型：
--
作者：
Kavanagh DH;Savage DA;Patterson CC;McKnight AJ;Crean JK;Maxwell AP;McKay GJ;Warren 3/UK GoKinD Study Group
肾间质纤维化和肾小球硬化是糖尿病肾病（DN）的标志，一些研究表明WNT通路成员参与了这些病理过程。本研究全面检查了WNT通路中与DN相关的常见遗传变异。在GENIE荟萃分析数据集中，根据名义显著性和一致的效应方向选择WNT通路内的基因。在1型糖尿病白人人群中，研究了WNT通路基因中常见的snp和常见的单倍型，与DN不一致（病例：n = 718；对照组：n = 749）。使用Sequenom或Taqman法对snp进行基因分型。使用PLINK进行关联分析，比较病例和对照组的等位基因和单倍型频率。通过置换检验或使用错误发现率对多重检验进行校正。包括采集中心、糖尿病病程和平均糖化血红蛋白为变量的logistic回归模型显示，GSK3B中的3个snp （rs17810235、rs17471、rs334543）、DAAM1中的2个snp （rs1253192、rs1252906）和NFAT5中的1个snp （rs17297207）与DN显著相关（P < 0.05），但经过多次检验校正后，这些snp并不显著。以ESRD为结果的单倍型Logistic回归和两两相互作用分析在多次检验校正后没有产生任何显著结果。这些结果表明，WNT通路基因的常见snp和常见单倍型与DN的相关性不强。然而，这并不能完全排除这些或WNT通路与DN的关联，因为未知的罕见遗传或拷贝数变异仍然可能对DN的遗传结构有贡献。
Renal interstitial fibrosis and glomerular sclerosis are hallmarks of diabetic nephropathy (DN) and several studies have implicated members of the WNT pathways in these pathological processes. This study comprehensively examined common genetic variation within the WNT pathway for association with DN. Genes within the WNT pathways were selected on the basis of nominal significance and consistent direction of effect in the GENIE meta-analysis dataset. Common SNPs and common haplotypes were examined within the selected WNT pathway genes in a white population with type 1 diabetes, discordant for DN (cases: n = 718; controls: n = 749). SNPs were genotyped using Sequenom or Taqman assays. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Correction for multiple testing was performed by either permutation testing or using false discovery rate. A logistic regression model including collection centre, duration of diabetes, and average HbA1c as covariates highlighted three SNPs in GSK3B (rs17810235, rs17471, rs334543), two in DAAM1 (rs1253192, rs1252906) and one in NFAT5 (rs17297207) as being significantly (P < 0.05) associated with DN, however these SNPs did not remain significant after correction for multiple testing. Logistic regression of haplotypes, with ESRD as the outcome, and pairwise interaction analyses did not yield any significant results after correction for multiple testing. These results indicate that both common SNPs and common haplotypes of WNT pathway genes are not strongly associated with DN. However, this does not completely exclude these or the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could still contribute towards the genetic architecture of DN.
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影响因子：
10.5
作者：
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通讯作者：
Maxwell AP
DOI：
10.1152/ajprenal.00326.2007
发表时间：
2008-05-01
影响因子：
4.2
作者：
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通讯作者：
Matsell, Douglas G.
影响因子：
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通讯作者：
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