Syndecan-4 is a candidate gene for diabetic nephropathy

Chinese Journal of Nephrology ›› 2012, Vol. 28 ›› Issue (4) : 312-317.

基础研究

FAN Qiu-ling, LI Sha-li, PU Shi, GUO Jia-yin, YUE Yuan, ZHANG Yu-xia, FENG Jiang-min, MA Jian-fei, JIANG Yi, WANG Li-ning.

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Objective To identify the candidate genes in the vicinity of a susceptibility locus(urinary albumin 1, UA-1) contributing to the development of albuminuria in type 2 diabetic KK/Ta mice. Methods Total RNA was extracted from the kidneys of KK/Ta (n=3) and BALB/c (n=2) mice at 20 weeks of age. The gene expression profile in kidney was investigated using the Affymetrix Murine Genome U74Av2 array. Competitive RT-PCR was used to confirm the differential expression of syndecan-4 which located in the vicinity of UA-1. Genome DNA was extracted from KK/Ta and BALB/c mice. DNA sequence analysis of the coding and promotor region of syndecan-4 gene was conducted. Results In the vicinity of the susceptibility locus (UA-1) contributing to the development of albuminuria in type 2 diabetic KK/Ta mice, 10 candidate genes that showed differential expression were identified. Among them, the gene expression of syndecan-4 in KK/Ta kidneys at 20 weeks of age was up-regulated by 26.1 times of age-matched BALB/c kidneys. Sequence analysis revealed two synonymous polymorphisms in the coding region (A93C and T216C) and three polymorphisms in the promoter region (-T263C, -T396C and -G669A) of the syndecan-4 gene. The TATA box was found at 321 bp upstream from the transcription start site, and the T263C polymorphism was located in the binding site of transcription factor Clox. Conclusions Syndecan-4 gene is mapped in the vicinity of the susceptibility locus contributing to the development of albuminuria in type 2 diabetes. The gene expression of syndecan-4 in KK/Ta kidneys is up-regulated than that in age-matched BALB/c kidneys at 20 weeks of age. Thus syndecan-4 may be one of the potential candidate genes responsible for diabetic nephropathy. Sequence differences in the promoter region influence the expression levels of syndecan-4 genes in KK/Ta kidneys.

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Diabetic nephropathies / Polymorphism / single nucleotide / Candidate gene / KK/Ta mice / Syndecan-4

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FAN Qiu-ling;LI Sha-li;PU Shi;GUO Jia-yin;YUE Yuan;ZHANG Yu-xia;FENG Jiang-min;MA Jian-fei;JIANG Yi;WANG Li-ning. . Syndecan-4 is a candidate gene for diabetic nephropathy[J]. Chinese Journal of Nephrology, 2012, 28(4): 312-317.

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Received	Revised	Published
1900-01-01	1900-01-01	2012-04-15
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2012-04-15

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