1. Evaluation of Genetic Association and Expression Reduction of TRPC1 in the Development of Diabetic Nephropathy
- Author
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Elisabete A. dos Santos, Pamela J. Hicks, Milan Flekac, Barry I. Freedman, Dongying Zhang, Donald W. Bowden, Suad Efendic, Kerstin Brismar, and Harvest F. Gu
- Subjects
Adult ,Male ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Genotype ,Gene Expression ,Single-nucleotide polymorphism ,Bioinformatics ,Polymorphism, Single Nucleotide ,White People ,End stage renal disease ,Diabetic nephropathy ,TRPC1 ,Cohort Studies ,Mice ,Internal medicine ,medicine ,Animals ,Humans ,Diabetic Nephropathies ,Gene ,Genetic association ,Aged ,TRPC Cation Channels ,business.industry ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Chromosome ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Black or African American ,Mice, Inbred C57BL ,Endocrinology ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Nephrology ,Case-Control Studies ,Hypertension ,Kidney Failure, Chronic ,Female ,business ,Original Report: Laboratory Investigation - 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.
- Published
- 2008