Osteoporosis.  2012 Dec;10(3):112-118.

The Relationship between Wnt Antagonist Genes Polymorphisms and Changes in Production of Osteoprotegerin and Soluble Receptor Activator of NF-kB by Whole Blood Cells after Hormone Therapy

• Park KE
• Lee DO
• Kim H
• Ku SY
• Kim SH
• Choi YM
• Kim JG

Abstract

OBJECTIVES
To investigate the relationship between single nucleotide polymorphism (SNP)s in Wnt antagonist genes, and production of osteoprotegerin (OPG) and soluble receptor activator of NF-kappaB ligand (sRANKL) by whole blood cells after hormone therapy (HT) in postmenopausal Korean women.
MATERIALS AND METHODS
The Dkk1 c.318A>G, Dkk2 c.437G>A, Dkk3 c.1003A>G polymorphisms and sFRP3 c.970C>G, sFRP4 c.958C>A, and c.1019G>A polymorphisms, and sFRP5 c.20G>C polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), direct sequencing, and Taqman assay in 75 postmenopausal Korean women receiving estrogen-progestogen therapy. The production of OPG and sRANKL by lipopolysaccharide-stimulated whole blood cells (WBC) before and after HT of 6 months were also measured.
RESULTS
Changes in the production of OPG and sRANKL by lipopolysaccharide-stimulated WBC, and in ratios of sRANKL(x1,000)/OPG after HT of 6 months were not different according to SNPs in Wnt signal pathway genes except Dkk1 c.318A>G SNP. The AA genotype of Dkk1 c.318A>G SNP showed significantly higher changes (p<0.05) in ratios of sRANKL(x1,000)/OPG compared to other genotypes. There were no significant differences in changes in the production of OPG and sRANKL, and in ratios of sRANKL(x1,000)/OPG among combined genotypes of sFRP4 c.958C>A, and c.1019G>A polymorphisms after HT.
CONCLUSIONS
Dkk1 c.318A>G SNP are related with changes in ratios of sRANKL(x1,000)/OPG in terms of the production of OPG and sRANKL by lipopolysaccharide-stimulated whole blood cells after HT.

Keyword

Hormone therapy; Osteoprotegerin; Receptor activator of nuclear factor-kB ligand; Whole blood cell; Wnt antagonist polymorphism

MeSH Terms

Blood Cells
Female
Genotype
Humans
NF-kappa B
Osteoprotegerin
Polymorphism, Single Nucleotide
Receptor Activator of Nuclear Factor-kappa B
Signal Transduction
NF-kappa B
Osteoprotegerin
Receptor Activator of Nuclear Factor-kappa B