From Single Nucleotide Polymorphism to Transcriptional Mechanism: A Model for
FRMD3 in Diabetic Nephropathy.
Authors Martini S, Nair V, Patel SR, Eichinger F, Nelson RG, Weil EJ, Pezzolesi MG,
Krolewski AS, Randolph A, Keller BJ, Werner T, Kretzler M
Submitted By Matthias Kretzler on 7/10/2013
Status Published
Journal Diabetes
Year 2013
Date Published 7/1/2013
Volume : Pages 62 : 2605 - 2612
PubMed Reference 23434934
Abstract Genome-wide association studies have proven to be highly effective at defining
relationships between single nucleotide polymorphisms (SNPs) and clinical
phenotypes in complex diseases. Establishing a mechanistic link between a
noncoding SNP and the clinical outcome is a significant hurdle in translating
associations into biological insight. We demonstrate an approach to assess the
functional context of a diabetic nephropathy (DN)-associated SNP located in the
promoter region of the gene FRMD3. The approach integrates pathway analyses with
transcriptional regulatory pattern-based promoter modeling and allows the
identification of a transcriptional framework affected by the DN-associated SNP
in the FRMD3 promoter. This framework provides a testable hypothesis for
mechanisms of genomic variation and transcriptional regulation in the context of
DN. Our model proposes a possible transcriptional link through which the
polymorphism in the FRMD3 promoter could influence transcriptional regulation
within the bone morphogenetic protein (BMP)-signaling pathway. These findings
provide the rationale to interrogate the biological link between FRMD3 and the
BMP pathway and serve as an example of functional genomics-based hypothesis

Investigators with authorship
Matthias KretzlerUniversity of Michigan