GGPS1 Promoter Variant (rs3806394) Is Associated With Larger Simple Renal Cysts via Reduced GGPPS Expression

We are aimed at investigating the association between the size of simple renal cyst (SRC) and the expression of geranylgeranyl pyrophosphate synthase (GGPPS), which can induce renal cyst formation after its deletion.

Seventy-seven patients who received renal cyst decortication were enrolled. Clinical characteristics and tissue sections were collected. We used immunohistochemistry and immunofluorescence to detect the expression and location of GGPPS in SRC tissues. The relationship between GGPPS expression and renal cyst size was evaluated by multivariate linear regression analysis. The tagging SNPs located in GGPS1 promoter were identified and the effect of the rs3806394 locus variant on GGPS1 promoter activity was assessed.

Immunohistochemistry and Western blot analysis revealed that GGPPS expression was downregulated in SRC tissues and that the larger the renal cyst volume was, the lower the expression of GGPPS in the cyst lining epithelial. Multivariate linear regression analysis indicated that low GGPPS levels in SRCs were independently related to large SRC size. Additionally, we reported that the frequency of the rs3806394 variant located in the GGPS1 promoter increased in SRC patients. The variant of the rs3806394 locus could decrease the activity of the GGPS1 promoter.

A reduction in GGPPS expression in the cyst lining epithelium was associated with a risk of larger SRC size. The variant of the rs3806394 locus may be one of the reasons for the differential GGPPS expression in SRC tissues among the patients. These findings offer novel insights into the pathological mechanisms of SRC development.