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Title: Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals
Authors: Lim, S.C.
Liu, J.J.
Low, H.Q.
Morgenthaler, N.G.
Li, Y.
Yeoh, L.Y.
Wu, Y.S.
Goh, S.K.
Chionh, C.Y.
Tan, S.H.
Kon, Y.C.
Soon, P.C.
Bee, Y.M.
Subramaniam, T.
Sum, C.F.
Chia, K.S. 
Keywords: Candidate genes
Diabetic nephropathy
Issue Date: Jul-2009
Citation: Lim, S.C., Liu, J.J., Low, H.Q., Morgenthaler, N.G., Li, Y., Yeoh, L.Y., Wu, Y.S., Goh, S.K., Chionh, C.Y., Tan, S.H., Kon, Y.C., Soon, P.C., Bee, Y.M., Subramaniam, T., Sum, C.F., Chia, K.S. (2009-07). Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals. Diabetologia 52 (7) : 1343-1351. ScholarBank@NUS Repository.
Abstract: 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∈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. © 2009 Springer-Verlag.
Source Title: Diabetologia
ISSN: 0012186X
DOI: 10.1007/s00125-009-1368-x
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