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http://purl.uniprot.org/citations/19415232http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19415232http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

Evolving research suggests that common and rare alleles jointly constitute the genetic landscape of complex disease. We studied the association between 43 pathway-related candidate genes with 'intermediate phenotype' (i.e. corresponding plasma protein) and diabetic nephropathy in a customised microarray of 1,536 SNPs.

Methods

In this case-control study of type 2 diabetic Chinese individuals with and without diabetic nephropathy, cases (n = 545) were defined on the basis of a spot urinary albumin/creatinine ratio (ACR) > 113 mg/mmol; the value for controls (n = 503) was ACR < 3.3 mg/mmol. Genotyping was performed using Illumina GoldenGate assay.

Results

No single nucleotide polymorphism (SNP) remained significant in single locus analysis after correction for multiple testing. Therefore, we explored the best approximately 1% SNPs. Of these 13 SNPs, four clustered to a 5' end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04-4.06) (heterozygous) and 2.48 (1.27-4.83) (homozygous) (p = 0.0055). The haplotype was correlated with plasma Cu/Zn superoxide dismutase (SOD) concentration, suggesting increased oxidative burden. Endothelin-1 SNP (rs1476046G>A, frequency = 0.252) was correlated with plasma C-terminal pro-endothelin-1 concentrations with an estimated OR for diabetic nephropathy of (heterozygous) 1.26 (0.96-1.66) and (homozygous) 1.87 (1.13-3.12) (p = 0.0072). Nitric oxide synthase 1 (NOS1) 5' haplotype (TGTC frequency = 0.38) also revealed a suggestive association with diabetic nephropathy: heterozygous 1.26 (0.95-1.67), homozygous 1.57 (1.04-2.35) (p = 0.0073). A rare NADPH oxidase homologue 1 (NOX1)-coding non-synonymous SNP (Arg315His, frequency = 0.006) was found exclusively among cases.

Conclusions/interpretation

Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are needed."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.org/dc/terms/identifier"doi:10.1007/s00125-009-1368-x"xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Liu J.J."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Wu Y.S."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Lim S.C."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Tan S.H."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Morgenthaler N.G."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Chia K.S."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Goh S.K."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Subramaniam T."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Sum C.F."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Bee Y.M."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Chionh C.Y."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Kon Y.C."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Low H.Q."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Soon P.C."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/author"Yeoh L.Y."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/pages"1343-1351"xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/title"Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals."xsd:string
http://purl.uniprot.org/citations/19415232http://purl.uniprot.org/core/volume"52"xsd:string
http://purl.uniprot.org/citations/19415232http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19415232
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