Vitamin D receptor 3'-untranslated region polymorphisms: lack of effect on mRNA stability.
Allelic variation at the 3'-end of the vitamin D receptor (VDR) gene has been associated with a 3-5-fold increased risk of developing prostate cancer and with differences in bone mineralization. This genetic diversity does not alter the VDR protein structurally, but instead may be a marker(s) of other, nearby polymorphisms that influence message stability or translation. The work reported here was instigated to identify additional VDR 3'-UTR polymorphisms that may have functional significance and to then test whether these genetic variants alter message stability. Initially, four novel, frequently occurring sequence variants were identified that associated with two common haplotypes that were described previously. These common sequence variants were not found within three message-destabilizing elements that we mapped within the 3'-UTR of the vitamin D receptor mRNA. Furthermore, the two VDR 3'-UTR haplotypes conferred an identical half-life on a heterologous beta-globin reporter gene, in an in vitro assay. We therefore conclude that common polymorphisms within the VDR 3'-UTR do not influence message stability.
Durrin
L K
LK
Department of Preventive Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, MS44, Los Angeles, CA 90033-0800, USA.
Haile
R W
RW
Ingles
S A
SA
Coetzee
G A
GA
D020413:3' Untranslated Regions; D016475:3T3 Cells; D000483:Alleles; D000818:Animals; D014644:Genetic Variation; D006801:Humans; D007962:Leukocytes; D008297:Male; D051379:Mice; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D018167:Receptors, Calcitriol