Genetic variants associated with adult blood pressure and kidney function do not affect fetal kidney volume. The Generation R Study

Background: Smaller kidneys with reduced number of nephrons in early life lead to impaired kidney function and risk for hypertension and chronic kidney disease. These associations might be partly explained by common genetic variation. Aims: To assess the associations between common genetic variants, which have recently shown to be associated with blood pressure or kidney function, with fetal kidney volume. Study design: A prospective population based cohort study in Rotterdam, The Netherlands. Subjects: 855 children, followed from early fetal life onwards (born 2003-2005). Predictor: Common genetic variants previously associated with blood pressure or kidney function. Outcome measures: Combined third trimester fetal kidney volume. Results: After taking into account multiple testing, only rs12940887 (near ZNF652) was significantly associated with fetal kidney volume (β: 0.88 (95% CI: 0.40; 1.37) cm 3 per minor allele, P-value<0.001), but the effect showed the opposite direction as expected. The remaining common genetic variants were not associated with fetal kidney volume. We also did not find associations of genetic variants previously shown to affect newborn kidney volume, with third trimester fetal kidney volume. Conclusions: Our results suggest that common genetic variants, associated with kidney function or disease and blood pressure, do not affect the third trimester fetal kidney volume. Further studies are needed to elucidate the mechanisms underlying the associations between small kidney size and increased risks of hypertension and impaired kidney function in adulthood.

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