SRD5A1 Genetic Variation and Prostate Cancer Epidemiology
Abstract
The human steroid 5-alpha reductase type I gene (SRD5Al) was examined for genetic changes in four ethnic groups: African-Americans, Latinos, Caucasians, and Japanese-Americans SRD5Al was examined because its gene product encodes an enzyme that can reduce androgens, which are known to be involved in modulating prostate gland growth, maintenance, and differentiation. In an attempt to identify common single nucleotide polymorphisms (SNPs) and establish allele frequencies, leukocyte genomic DNA from 118 men (half normal controls and half diagnosed with prostate cancer) was examined for SRD5Al genetic variants. The open reading frame (5' and 3' untranslated regions (UTR), codons, and some intronic sequence) was sequenced, plus over one thousand base pairs upstream of the gene. Twenty-eight DNA changes were discovered along the length of the gene. Most SNPs were transitions (88%) but there was one single base deletion in the putative promoter (which was confirmed using restriction fragment length polymorphism). The six codon SNPs were silent; however, there was linkage disequilibrium between the two SNPs in exon 2, forming a haplotype. With the genetic screen of SRD5Al variants completed, functional testing of promoter and 3'UTR Variants are currently being assessed in cell lines for changes in promoter activity, RNA steady-state and, half-life.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA428280
Entities
People
- Troy J. Phipps
Organizations
- University of Southern California