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Evaluation of genetic association and expression reduction of TRPC1 in the development of diabetic nephropathy

Zhang, D (author)
Freedman, BI (author)
Flekac, M (author)
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Santos, E (author)
Karolinska Institutet
Hicks, PJ (author)
Bowden, DW (author)
Efendic, S (author)
Brismar, K (author)
Karolinska Institutet
Gu, HF (author)
Karolinska Institutet
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 (creator_code:org_t)
2008-09-19
2009
English.
In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 29:3, s. 244-251
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • <i>Background/Aims:</i> 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. <i>Methods:</i> 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. <i>Results:</i> 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. <i>Conclusions:</i> 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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