Association between osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women.
OBJECTIVE
To investigate the association between osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL (sRANKL) levels, and bone mineral density (BMD) in Korean postmenopausal women.


METHODS
The OPG gene A163G, G209A, T245G, and G1181C polymorphisms, the RANK gene C421T and C575T polymorphisms, and the RANKL rs12721445 and rs2277438 polymorphisms were analyzed in 385 Korean postmenopausal women. Levels of serum OPG, soluble RANKL, osteocalcin, C-telopeptide of type I collagen, parathyroid hormone, calcium, and phosphorus and BMD at the lumbar spine and femoral neck were measured.


RESULTS
The A163G, G209A, and T245G polymorphisms in the OPG gene were in complete linkage. The RANK C421T and C575T polymorphisms and the RANKL rs12711445 polymorphism were not observed. An association with BMD was found only for the OPG G1181C polymorphism, and BMD at the lumbar spine in women with the CC genotype was significantly higher than in women with the GC or GG genotype, with a C allele dose effect. In itself, the RANKL rs2277438 polymorphism was not related to BMD, but by combining the RANKL genotypes with the GC genotypes of the OPG G1181C polymorphism, the association with BMD at the lumbar spine became significant. No significant differences in the levels of any biochemical marker among genotypes of these polymorphisms were found.


CONCLUSIONS
The OPG gene G1181C polymorphism, alone and in combination with the RANKL rs2277438 polymorphism, was identified as a genetic factor associated with BMD of the lumbar spine in Korean women.
Kim
Jung Gu
JG
Department of Obstetrics and Gynecology, College of Medicine, and Clinical Research Institute, Seoul National University Hospital, Seoul, Korea. kimjg@plaza.snu.ac.kr
Kim
Jung Hwa
JH
Kim
Ja Yeon
JY
Ku
Seung Yup
SY
Jee
Byung Chul
BC
Suh
Chang Suk
CS
Kim
Seok Hyun
SH
Choi
Young Min
YM
D000368:Aged; D015519:Bone Density / Q000235:genetics*; D002118:Calcium / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D007723:Korea; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000235:genetics; D053244:Osteoprotegerin / Q000235:genetics*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011110:Polymorphism, Genetic; D053245:RANK Ligand / Q000235:genetics*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*
D024042:Collagen Type I; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D015675:Osteocalcin; D010758:Phosphorus; D002118:Calcium