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  • Title: Evaluation of genetic association and expression reduction of TRPC1 in the development of diabetic nephropathy.
    Author: Zhang D, Freedman BI, Flekac M, Santos E, Hicks PJ, Bowden DW, Efendic S, Brismar K, Gu HF.
    Journal: Am J Nephrol; 2009; 29(3):244-51. PubMed ID: 18802326.
    Abstract:
    BACKGROUND/AIMS: The TRPC1 gene on chromosome 3q22-24 resides within the linkage region for diabetic nephropathy (DN) in type 1 (T1D) and type 2 diabetes mellitus (T2D). A recent study has demonstrated that TRPC1 expression is reduced in the kidney of diabetic ZDF- and STZ-treated rats. The present study aimed to evaluate the genetic and functional role of TRPC1 in the development of DN. METHODS: Genetic association study was performed with two independent cohorts, including 1,177 T1D European Americans with or without DN from GoKinD population and 850 African-American subjects with T2D-associated end-stage renal disease (ESRD), or with hypertensive (non-diabetic) ESRD, and nondiabetic controls. Seven tag SNP markers derived from HapMap data (phase II) were genotyped. TRPC1 gene expression was examined using real time RT-PCR. RESULTS: No significant association of TRPC1 DNA polymorphisms with DN or ERSD was found in GoKinD and African-American populations. TRPC1 gene mRNA expression in kidney was found to be trendily reduced in 12-week and significantly in 26-week-old db/db mice. CONCLUSIONS: TRPC1 genetic polymorphism may not fundamentally contribute to the development of DN, while reduction of the gene expression in kidney may be a late phenomenon of DN as seen in diabetic animal models.
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