Mutational Analysis of the TRPC6 Gene in Czech Adult Patients with Steroid-sensitive and Steroid-resistant Idiopathic Nephrotic Syndrome


Jana Reiterová (1, 2), Lena Obeidová (2), Jitka Štekrová (2), Petr Lněnička (2), Vladimír Tesař (1)


  1. Klinika nefrologie 1. LF UK a VFN, Praha
  2. Laboratoř molekulární diagnostiky, ÚBLG 1. LF UK a VFN, Praha

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are frequent causes of nephrotic syndrome (NS). About 50% of patients are resistant to immunosuppresive therapy and progress to chronic renal insufficiency. TRPC6 mutations are the cause of idiopatic NS in about 2-7 % of steroid-resistant  patients. 11 different TRPC6 gene mutations were identified. These mutations leads to a late onset kidney disease and a variable rate of progression to end stage renal disease. The aim of the study was the identification of mutations/polymorphisms in adult patients with FSGS/MCD in the Czech Republic.
Patients and methods: 40 patients (22 females, 18 males) with steroid- resistant FSGS/MCD and 44 patients  (22 females, 22 males) with steroid-sensitive FSGS/MCD were studied. Renal biopsy with the histological finding of FSGS/MCD was performed in the years 2004-2008. The mean age of the onset of NS was 39±20.7 years. Family history for proteinuria was positive in 3 patients. 300 healthy Czech individuals formed control group with mean age 58.4±19.5 years. High resolution melting analysis (HRM) was established for all 13 exons and intron-exon boundaries of the TRPC6 gene. Suspected samples were analysed by direct sequencing on ABI Prism™ 3130 and by amplicon sequencing on Roche GS Junior.
Results: Two polymorphisms were described: in exon 1 C43T (P15S) with prevalence 32.5% of heterozygotes and in exon 4 C1211T (A404V) with prevalence 20% of heterozygotes (1% of T/T homozygotes) in patients with steroid-resistant FSGS/MCD. The prevalence of heterozygotes in steroid-sensitive patients was 13.9% for C43T polymorphism and 29.5% for C1211T polymorphism. The prevalence of heterozygotes in control group was 16.5% for C43T and 20.5% for C1211T (2.5% of T/T homozygotes). T allele of C43T polymorphism in exon 1 was significantly more frequent in patients with steroid-resistant FSGS/MCD (χ2, p<0.05).
Conclusions: TRPC6 gene mutations are rare causes of  FSGS/MCD in adult patients in Czech Republic. The C43T polymorphism could have some influence on the therapeutic response  and progression of the disease.
Supported by grant project IGA NS 9779-4 and by research project ZZ MSMT 0021620806.

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