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Wnt 길항제 유전자 다형성과 호르몬 치료 후 전혈세포에서의 Osteoprotegerin 및 Soluble Receptor Activator of NF-kB Ligand 생산 변화 양상 사이의 연관성

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

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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-κB 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 sRANKLx1,000/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 sRANKLx1,000/OPG compared to other genotypes. There were no significant differences in changes in the production of OPG and sRANKL, and in ratios of sRANKLx1,000/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 sRANKLx1,000/OPG in terms of the production of OPG and sRANKL by lipopolysaccharide-stimulated whole blood cells after HT.

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-κB 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 sRANKLx1,000/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 sRANKLx1,000/OPG compared to other genotypes. There were no significant differences in changes in the production of OPG and sRANKL, and in ratios of sRANKLx1,000/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 sRANKLx1,000/OPG in terms of the production of OPG and sRANKL by lipopolysaccharide-stimulated whole blood cells after HT.

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