The association between polymorphisms in Wnt antagonist genes and bone response to hormone therapy in postmenopausal Korean women.
OBJECTIVE
The aim of this study was to explore the association between polymorphisms in Wnt antagonist genes and bone response to hormone therapy (HT) in postmenopausal Korean women.


METHODS
A prospective study was conducted with 303 postmenopausal women receiving sequential estrogen plus progestogen therapy in a university hospital. The dickkopf (Dkk) 1 c.318A>G, Dkk2 c.437G>A, Dkk3 c.1003A>G, secreted frizzled-related protein (sFRP) 1 rs3242C>T, rs16890444C>T, sFRP3 c.970C>G, sFRP4 c.958C>A, c.1019G>A, and sFRP5 c.20G>C polymorphisms were analyzed, and bone mineral density (BMD) at the lumbar spine and femoral neck (FN) was measured before and after 1 year of sequential estrogen plus progestogen therapy.


RESULTS
The percentage changes in BMD of the FN after 1 year of HT were found to be significantly (P < 0.05) different according to the haplotype genotype composed of the sFRP4 c.958C>A and c.1019G>A polymorphisms after adjustment for baseline BMD. The percentage change in BMD at the FN after 1 year of HT was significantly higher in the AA/AG haplotype genotype than in the AG/CG (P < 0.01) or CG/CG (P < 0.05) haplotype genotype. However, any single and combined polymorphisms measured were not related with nonresponsiveness to HT when a nonresponder was defined as a woman who had lost more than 3% of BMD per year after HT.


CONCLUSIONS
The haplotype genotypes of sFRP4 c.958C>A and c.1019G>A polymorphisms are genetic factors that affect changes in BMD of the FN after HT in postmenopausal Korean women.
Department of Obstetrics and Gynecology, Incheon Medical Center, Incheon, Korea.
Hoon
H
Kim
Dong Ock
DO
Lee
Seung-Yup
SY
Ku
Seok Hyun
SH
Kim
Jong Hak
JH
Kim
Jung Gu
JG
Kim
D015519:Bone Density / Q000187:drug effects* / Q000235:genetics; D015914:Estrogen Replacement Therapy; D005260:Female; D005272:Femur Neck; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007723:Korea; D008159:Lumbar Vertebrae; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics; D053244:Osteoprotegerin / Q000097:blood; D011110:Polymorphism, Genetic / Q000235:genetics*; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D000099274:Frizzled-Related Proteins; D000094742:Secreted Frizzled-Related Proteins
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D011372:Progestins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins; C501126:DKK1 protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins