Dopamine D1 receptor (DRD1) genetic polymorphism: Pleiotropic effects on heritable renal traits

16Citations
Citations of this article
25Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Because dopamine D 1 receptors (DRD1) influence renal sodium transport and vascular hemodynamics, we examined whether genetic polymorphisms play a role in renal function. We conducted polymorphism discovery across the DRD1 open reading frame and its 5′-UTR and then performed association studies with estimated glomerular filtration rate (eGFR), plasma creatinine (pCr), and fractional excretion of uric acid (FeUA). We used a twin/family group of 428 subjects from 195 families and a replication cohort of 677 patients from the Kaiser health-care organization sampled from the lower percentiles of diastolic blood pressures. Although the coding region lacked common non-synonymous variants, we identified two polymorphisms in the DRD1 5′-UTR (G-94A, A-48G) that occurred with frequencies of 15 and 30%, respectively. In the twin/family study, renal traits were highly heritable, such that DRD1 G-94A significantly associated with eGFR, pCr, and FeUA. Homozygotes for the G-94A minor allele (A/A) exhibited lower eGFR, higher pCr, and lower FeUA. No effects were noted for DRD1 A-48G. Patients in the Kaiser group had similar effects of G-94A on eGFR and pCr. Kidney cells transfected with the-94A variant but not the wild type vectors had increased receptor density. Because the-94A allele is common and may reduce glomerular capillary hydrostatic pressure, G-94A profiling may aid in predicting survival of renal function in patients with progressive renal disease. © 2009 International Society of Nephrology.

Cite

CITATION STYLE

APA

Fung, M. M., Rana, B. K., Tang, C. M., Shiina, T., Nievergelt, C. M., Rao, F., … O’Connor, D. T. (2009). Dopamine D1 receptor (DRD1) genetic polymorphism: Pleiotropic effects on heritable renal traits. Kidney International, 76(10), 1070–1080. https://doi.org/10.1038/ki.2009.306

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free