| Summary: | 博士 === 國立清華大學 === 生命科學系 === 91 === Abstract
Osteoporosis is a multifactorial disease and a common disorder with a strong genetic component. The exact molecular mechanism of the abnormal biomineralization is still unclear. However, biomolecules are proposed to play a role. In this study, we aimed to investigate the molecular biological mechanism of osteoporosis.
We determined the vitamin D receptor gene intron 8 BsmI and start codon FokI polymorphisms, HindIII osteocalcin gene polymorphism, Alu I calcitonin receptor gene polymorphism, interleukin-1β(promoter and exon 5) and interleukin-1 receptor antagonist (intron 2) gene polymorphisms, —308 tumor necrosis factor-αpolymorphism, CYP 17 5’-UTPR polymorphism, and urokinase 3’-UTR gene polymorphism, using polymerase chain reaction-based restriction analysis in postmenopausal Chinese women in Taiwan. The estrogen receptor gene microsatellite polymorphism and androgen receptor α gene microsatellite polymorphism were determined using polymerase chain reaction-based microsatellite analysis. Bone mineral density of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry.
The present study shows: 1) the vitamin D receptor gene intron 8 BsmI polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis; 2) the FokI vitamin D receptor gene polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis at the lumbar spine; 3) the Hind III osteocalcin gene polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis at the femoral neck; 4) the Alu I calcitonin receptor gene polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis; 5) the Taq I interleukin-1βexon 5 gene polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis at the lumbar spine; 6) the estrogen receptor αgene microsatellite polymorphism and the androgen receptor gene microsatellite polymorphism are associated with reduced bone mineral density and predisposes women to osteoporosis at the femoral neck. Our results show that the Ava I interleukin-1β promoter, VNTR intron 2 interleukin-1 receptor antagonist, —308 tumor necrosis factor-α, CYP 17 5’-UTPR, and urokinase 3’-UTR gene polymorphisms are not related to low bone mineral density and susceptibility to osteoporosis at the lumbar spine and the femoral neck.
In conclusion, the results of our study suggest that the BsmI intron 8 vitamin D receptor gene, FokI start codon vitamin D receptor gene, Hind III osteocalcin gene, Alu I calcitonin receptor gene, Taq I interleukin-1βexon 5 gene, estrogen receptor αgene microsatellite, and androgen receptor gene microsatellite polymorphisms may be candidate genetic markers for osteoporosis in postmenopausal women. Further study of other possible genetic markers with regard to osteoporosis might provide new information to the genetic background underlying bone mineral density in women.
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