Evaluation of genetic association and expression reduction of TRPC1 in the development of diabetic nephropathy.
OBJECTIVE
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.
Zhang
Dongying
D
Rolf Luft Center for Diabetes Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
Freedman
Barry I
BI
Flekac
Milan
M
Santos
Elisabete
E
Hicks
Pamela J
PJ
Bowden
Donald W
DW
Efendic
Suad
S
Brismar
Kerstin
K
Gu
Harvest F
HF
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications*; D007676:Kidney Failure, Chronic / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D050052:TRPC Cation Channels / Q000235:genetics*; D044465:White People / Q000235:genetics
D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1