Distribution and functional consequences of nucleotide polymorphisms in the 3′-untranslated region of the human Sep15 gene

Document Type

Article

Publication Date

3-1-2001

Abstract

Selenium has been shown to prevent cancer in a variety of animal model systems. Both epidemiological studies and supplementation trials have supported its efficacy in humans. However, the mechanism by which selenium suppresses tumor development remains unknown. Selenium is present in known human selenoproteins as the amino acid selenocysteine (Sec). Sec is inserted cotranslationally in response to UGA codons within selenoprotein mRNAs in a process requiring a sequence within the 3′-untranslated region (UTR), referred to as a Sec insertion sequence (SECIS) element. Recently, a human Mr 15, 000 selenoprotein (Sep15) was identified that contains an in-frame UGA codon and a SECIS element in the 3′-UTR. Examination of the available cDNA sequences for this protein revealed two polymorphisms located at position 811 (C/T) and at position 1125 (G/A) located within the 3′-UTR. Here, we demonstrate significant differences in Sep15 allele frequencies by ethnicity and that the identity of the nucleotides at the polymorphic sites influences SECIS function in a selenium-dependent manner. This, together with genetic data indicating loss of heterozygosity at the Sep15 locus in certain human tumor types, suggests that Sep15 may be involved in cancer development, risk, or both.

Publication Source (Journal or Book title)

Cancer Research

First Page

2307

Last Page

2310

This document is currently not available here.

Share

COinS