Identification of a mutation in the human raloxifene response element of the transforming growth factor-3 gene.
10.3346/jkms.2001.16.5.549
- Author:
Ki Ok HAN
1
;
Young Soon KANG
;
Chang Sun HWANG
;
In Gul MOON
;
Chang Hoon YIM
;
Ho Yeun CHUNG
;
Hak Chul JANG
;
Hyun Koo YOON
;
In Kwon HAN
;
Young Kil CHOI
Author Information
1. Department of Internal Medicine, Samsung Cheil Women's Healthcare Center and Hospital, Sungkyunkwan University School of Medicine.
- Publication Type:Original Article
- Keywords:
Transforming Growth Factor-beta3;
Raloxifence;
Response Elements;
Mutation
- MeSH:
Estrogen Antagonists/*pharmacology;
Female;
Human;
Middle Age;
*Mutation;
Raloxifene/*pharmacology;
*Response Elements;
Transfection;
Transforming Growth Factor beta/*genetics
- From:Journal of Korean Medical Science
2001;16(5):549-552
- CountryRepublic of Korea
- Language:English
-
Abstract:
The human transforming growth factor-3 (TGF-3) is an important cytokine to maintain bone mass by inhibiting osteoclast differentiation. Recently raloxifene response element (RRE), a new enhancer with a polypurine sequence for estrogen receptor (ER)-mediated gene activation, was identified on the TGF-3 gene. Functional analysis of the RRE-mediated pathway has shown that this would be an important pathway for bone preserving effect. We found a novel mutation in the RRE sequence by single-strand conformational polymorphism analysis in one of 200 Korean women. Cloning and sequencing revealed a heterozygote in which one allele had an insertion of 20 nucleotides (AGAGAGGGAGAGGGAGA GGG) between nucleotide +71 and +72 and a point mutation at nucleotide +75 (G-A transition), and the other allele had normal sequence. The insertion was a nearly perfect tandem duplication of the wild type DNA sequence. The bone mineral density of the affected woman was not much lower than that of age-matched controls. Transient transfection of the mutant allele showed no significantly different activity compared with that of the wild type allele. These observations suggest that the heterozygote variation of the RRE sequence seems not to be operative in determination of bone mass.
