Syndecan-4 is a candidate gene for diabetic nephropathy
10.3760/cma.j.issn.1001-7097.2012.04.013
- VernacularTitle:多配体蛋白聚糖4是糖尿病肾病的候选基因
- Author:
Qiuling FAN
;
Shali LI
;
Shi PU
;
Jiayin GUO
;
Yuan YUE
;
Yuxia ZHANG
;
Jiangmin FENG
;
Jianfei MA
;
Yi JIANG
;
Lining WANG
- Publication Type:Journal Article
- Keywords:
Diabetic nephropathies;
Polymorphism,single nucleotide;
Candidate gene;
KK/Ta mice;
Syndecan-4
- From:
Chinese Journal of Nephrology
2012;28(4):312-317
- CountryChina
- Language:Chinese
-
Abstract:
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-4in 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.
