ArticleDiabetologia2009
Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals.
Article in Diabetologia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 20 citations in OpenAlex.
- Oxidative Stress-Related Gene Polymorphisms Are Associated With Hepatitis B Virus-Induced Liver Disease in the Northern Chinese Han Population.Frontiers in genetics · 2019Article
- Complement 7 Is Up-Regulated in Human Early Diabetic Kidney Disease.The American journal of pathology · 2018Article
- A Case-Control Study of the Genetic Variability in Reactive Oxygen Species-Metabolizing Enzymes in Melanoma Risk.International journal of molecular sciences · 2018Article
- Genetics of cardiovascular and renal complications in diabetes.Journal of diabetes investigation · 2016Review
- Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C.European journal of medical research · 2015Article
- Article
- Genome-wide association studies of chronic kidney disease: what have we learned?Nature reviews. Nephrology · 2011Review
- Genetics of chronic kidney disease.Nephron. Clinical practice · 2011Article
- Phosphodiesterase-5 gene (PDE5A) polymorphisms are associated with progression of childhood IgA nephropathy.Pediatric nephrology (Berlin, Germany) · 2010Article
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16 authors at 5 institutions in 1 country.
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Abstract
aims/hypothesisEvolving 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.
methodsIn 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.
resultsNo 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/
interpretationOur 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.
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