한국 폐경여성에서 calcitonin 수용체 유전자 AluI 다형성과 골밀도 및 호르몬 대체요법에 대한 골 반응도사이의 연관성
The relationship between calcitonin receptor gene AluI polymorphism, bone mineral density and bone responsiveness to hormone replacement therapy in postmenopausal Korean women
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목적: 한국 폐경여성에서 CTR 유전자 다형성양상과 골밀도 및 호르몬치료후 골반응도사이에 연관성이 있는가를 알아보고자 하였다. 연구 방법: 자연폐경여성 433명과 이들 중 주기적 호르몬 대체요법을 1년간 받은 자연폐경여성 306명을 대상으로 하여 CTR 유전자 AluI 다형성양상을 RFLP으로 분석하였고 요추 및 대퇴 근위부에서의 골밀도를 호르몬치료전과 치료 후 1년에서 DXA로, 혈청 CTX, osteocalcin, BAP, calcitonin를 면역측정법으로 측정하였다. 결과: CTR 유전자형 CC, CT, TT의 분포는 각각 81.3%, 17.5%. 1.2% 이었다. CTR 유전자형에 따른 요추, 근위 대퇴부에서의 골밀도 및 호르몬 대체요법 1년 후 골밀도의 변화양상의 차이가 없었다. 또한 이런 유전자형에 따른 혈청 calcitonin과 골교체인자 농도의 차이가 없었고 호르몬 대체요법 6개월 후 이들 인자의 변화양상도 차이가 없었다. 정상골밀도 여성, 골감소증 여성과 골다공증여성사이 및 호르몬 대체요법 반응군과 비반응군 (년간 골량이 3% 이상 손실) 사이에 각 CTR유전자형의 분포양상의 차이가 없었다. 결론: 한국여성에서 CTR AluI 유전자다형성은 골밀도와 호르몬치료후 골밀도 변화에 영향을 미치지 않는다.
Abstract
Objective: To evaluate the relationship between the calcitonin receptor (CTR) gene AluI polymorphism, serum calcitonin levels, bone mineral density (BMD) and bone responsiveness to hormone replacement therapy (HRT). Methods: The CTR AluI polymorphism were determined by restriction fragment length polymorphism (RFLP) in 433 postmenopausal Korean women. Among these women, 306 women received sequential HRT for 1 year. Serum bone alkaline phosphatase, CrossLaps, osteocalcin and calcitonin levels were measured by immunoassay and BMD at the lumbar spine and proximal femur by dual energy X-ray absorptiometry before and after HRT of 1 year. Results: The CTR genotype frequencies were 81.3% for CC, 17.5% for CT, and 1.2% for TT. No significant differences in BMD at the lumbar spine and proximal femur and their annual percentage changes after HRT were noted among CTR genotypes. There were no significant differences in the levels of calcitonin or bone turnover markers and their 6 month percentage changes after HRT among CTR genotypes. The CTR genotypes were not distributed differently between HRT-responders and HRT-nonresponders (women who lose more than 3% of bone mass per year) or between women with normal BMD and women with low bone mass. Conclusion: The CTR AluI polymorphism is not associated with BMD and bone responsiveness to HRT in Korean women.
참고문헌 (34)
- Osteoporosis prevention, "diagnosis, and therapy. NIH Consens Statement", 17, pp.1~45 (2000)
- Jouanny P, "Environmental and genetic factors affecting bone mass:Similarity of bone density among members of healthy families", 38, pp.61~7 (1995)
- Zmuda JM, "Recent progress in understanding the genetic susceptibility to osteoporosis", 16, pp.356~67 (1999)
- Brown M, "The genetics of osteoporosis:future diagnostic possibilities", 20, pp.527~47 (2000)
- Stewart TL, "Role of genetic factors in the pathogenesis of osteoporosis", 166, pp.235~45 (2000)
- Kim JG, "Association of vitamin D receptor and estrogen receptor gene polymorphisms with bone mass in postmenopausal Korean women", 8, pp.222~8 (2001)
- 김정구, "한국 폐경여성에서 비타민 D 수용체 유전자 다형성과 골밀도의 연관성", Obstetrics & Gynecology Science, 45(11), pp.15~15 (2002), 대한산부인과학회
- 김정구, "한국 폐경여성에서 비타민 D 수용체 유전자내 poly 다형성과 골밀도의 연관성", 46, pp.795~801 (2003)
- Kim JG, "The relationship among serum insulin-like growth factor-I insulin-like growth factor-I gene polymorphism and bone mineral density in postmenopausal women in Korea", 186, pp.345~350 (2002)
- Hoff AO,, "Calcitonin. In: Marcus R, Feldman D, Kelsey J editors. Osteoporosis.", pp.247~55 (2001), Academic Press
- Gorn AH, "and expression of a human calcitonin receptor from an ovarian carcinoma cell line", pp.1726~35
- Shyu JF, "The deletion of 14 amino acids in the seventh transmembrane domain of a naturally occurring calcitonin receptor isoform alters ligand binding and selectively abolishes coupling to phospholipase C", 271, pp.31127~34 (1996)
- Nussenzveig DR, "Alternative splicing of a 48-nucleotide exon generates two isoforms of the human calcitonin receptor", 136, pp.2047~51 (1995)
- Nakamura, "Allelic variants of human calcitonin receptor in the Japanese population", 99, pp.38~41 (1997)
- Nakamura M, "Calcitonin receptor gene polymorphism in Japanese women:correlation with body mass and bone mineral density", 68, pp.211~5 (2001)
- Masi, "Allelic variants of the human calcitonin receptor distribution and association with bone mass in postmenopausal Italian women", 245, pp.622~6 (1998)
- Taboulet J, "Cacitonin receptor polymorphism is associated with a decreased fracture risk in postmenopausal women", 7, pp.2129~33 (1998)
- Zolfkova I, "Lack of association between AluI polymorphism of calcitonin receptor gene and bone mass in Czech postmenopausal women", 28, pp.133~ (2001)
- Braga V, "Association of CTR and COLIA1 alleles with BMD values in peri- and postmenopausal women", 67, pp.361~6 (2000)
- Hassager C, "Non-responders to hormone replacement therapy for the prevention of postmenopausal bone loss:Do they exist?", 4, pp.36~41 (1994)
- Rozenberg S, "Decrease of bone mineral density during estrogen substitution therapy", 17, pp.205~10 (1993)
- Kurabayashi T, "Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women", 180, pp.1115~20 (1999)
- Deng HW, "Change of bone mass in postmenopausal Caucasian women with and without hormone replacement therapy is associated with vitamin D receptor and estrogen receptor genotypes", 103, pp.576~85 (1998)
- Giguere Y, "The association between heel ultrasound and hormone replacement therapy is modulated by a two-locus vitamin D and estrogen receptor genotype", 15, pp.1076~84 (2000)
- Kanis JA, "The diagnosis of osteoporosis", 9, pp.1137~41 (1994)
- Vandevyver C, "Influence of Vitamin D receptor gene alleles on bone mineral density in postmenopausal and osteoporotic women", 12, pp.241~7 (1997)
- Gomez C, "bone loss and prevalence of vertebral fracture differences in postmenopausal women and men", 10, pp.175~82 (1999), bone mass
- Cron P, "and chromosomal localization of the porcine calcitonin receptor gene Identification of two variants of the receptor generated by alternative splicing"
- Yamin M, "Cloning and characterization of a mouse brain calcitonin receptor complementary deoxyribonucleic acid and mapping of the calcitonin receptor gene", 135, pp.2635~43 (1994)
- Sarkar A, "and expression of a calcitonin receptor from guinea pig brain", 69, pp.455~64 (1997)
- Shenker A, "G protein-coupled receptor structure and function:the impact of disease-causing mutations", 9, pp.427~51 (1995)
- Kremer H, "Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene", 9, pp.160~4 (1995)
- Smith EP, "Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man", 331, pp.1056~61 (1994)
- Reihsaus E, "Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects", 8, pp.334~9 (1993)
