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    ๅœฐๆ–น่‡ชๆฒปๅœ˜้ซ”์˜ ่กŒๆ”ฟๆฑบๅฎšๆฌŠ้™์˜ ้…ๅˆ†ๆง‹้€ ์— ๊ด€ํ•œ ็ก็ฉถ : ไธ€่ˆฌ็š„ ็‰นๆ€ง ๋ฐ ๅœฐๆ–น่‡ชๆฒปๅœ˜้ซ”้•ท์˜ ๅ‡บ่บซ่ƒŒๆ™ฏ์„ ๅๆ˜ ํ•œ ็ก็ฉถ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ํ–‰์ •๋Œ€ํ•™์› :ํ–‰์ •ํ•™๊ณผ ํ–‰์ •ํ•™์ „๊ณต,2000.Maste

    Relationship between polymorphisms of Wnt antagonists genes, osteoprotegerin, receptor activator of NF-kB in circulating system and bone mineral density in postmenopausal Korean women

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์˜ํ•™๊ณผ ์‚ฐ๋ถ€์ธ๊ณผํ•™, 2012. 8. ๊น€์ •๊ตฌ.์„œ๋ก : ํ•œ๊ตญ ํ๊ฒฝ์—ฌ์„ฑ์—์„œ Wnt ๊ธธํ•ญ๋ฌผ์งˆ๊ณ„ ์œ ์ „์ž๋‚ด ๋‹คํ˜•์„ฑ๊ณผ ๊ณจ๋ฐ€๋„, ์ˆœํ™˜๊ณ„ ๋‚ด ๊ณจ๊ต์ฒด์ธ์ž ๋ฐ receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ์‚ฌ์ด์— ์—ฐ๊ด€์„ฑ์ด ์žˆ๋Š”๊ฐ€๋ฅผ ๋ถ„์„ํ•˜์—ฌ Wnt ๊ธธํ•ญ๋ฌผ์งˆ๊ณ„ ์œ ์ „์ž๋‚ด ๋‹คํ˜•์„ฑ์ด ๊ณจ๋‹ค๊ณต์ฆ์ด ๋ฐœ์ƒํ•  ์œ„ํ—˜์ด ์žˆ๋Š” ํ๊ฒฝ์—ฌ์„ฑ์„ ์˜ˆ์ธกํ•  ์ˆ˜ ์žˆ๋Š” ์ƒˆ๋กœ์šด ์ง€์นจ์ž๋กœ์„œ ์‚ฌ์šฉ๋  ๊ฐ€๋Šฅ์„ฑ์ด ์žˆ๋Š”์ง€ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜์˜€๋‹ค. ๋ฐฉ๋ฒ•: ์ž์—ฐํ๊ฒฝ ํ›„ ํ•œ๊ตญ์—ฌ์„ฑ 399๋ช…์—์„œ Wnt ์–ต์ œ์ธ์ž (Wnt inhibitory factor: WIF), secreted frizzled-related-protein (SFRP)1, SFRP2, SFRP3, SFRP4, SFRP5, Dickkopf (DKK)1, DKK2, DKK3 ์œ ์ „์ž์—์„œ ์ด 19๊ฐ€์ง€ ๋‹จ์ผ๋‰ดํด๋ ˆ์˜คํ‹ฐ๋“œ๋‹คํ˜•์„ฑ (single nucleotide polymorphism: SNP)์„ ์ œํ•œํšจ์†Œ์กฐ๊ฐ๊ธธ์ด๋‹คํ˜•์„ฑ, ์—ผ๊ธฐ์„œ์—ด๋ถ„์„๊ณผ Taqman ์ธก์ •๋ฒ• ๋“ฑ์„ ์ด์šฉํ•˜์—ฌ ๋ถ„์„ํ•˜๊ณ  Wnt ๊ธธํ•ญ๋ฌผ์งˆ๊ณ„ ์œ ์ „์ž๋‚ด ๋‹จ๋… ๋˜๋Š” ๋ณตํ•ฉ ๋ณ€์ด ์–‘์ƒ์— ๋”ฐ๋ฅธ ๊ณจ๋ฐ€๋„๋ฅผ ๋ถ„์„ํ•˜๊ณ  ์—ญ์œผ๋กœ ๊ณจ๋ฐ€๋„ ์–‘์ƒ์— ๋”ฐ๋ฅธ ์ด๋Ÿฌํ•œ ์œ ์ „์ž๋“ค์˜ ๋ถ„ํฌ๋ฅผ ๋ถ„์„ํ•˜๋ฉฐ ์ˆœํ™˜๊ณ„์—์„œ์˜ OPG, ์šฉ์งˆ์„ฑ RANKL (soluble RANKL: sRANKL) ๋†๋„, ๊ณจ๊ต์ฒด์ธ์ž์™€์˜ ์—ฐ๊ด€์„ฑ์„ ๋น„๊ต๋ถ„์„ํ•˜์˜€๋‹ค. ๊ฒฐ๊ณผ 1) WIF-1 ์œ ์ „์ž๋‚ด c.28G>A, c.496C>A, SFRP2 ์œ ์ „์ž๋‚ด c.-38C>G, c.134C>T, SFRP3 ์œ ์ „์ž๋‚ด c.598C>T, SFRP5 ์œ ์ „์ž ๋‚ด c.34A>T, c.35C>A, DKK3 ์œ ์ „์ž๋‚ด c.92C>A, c.147G>A, c.706G>A์—์„œ SNP๋Š” ๊ด€์ฐฐ๋˜์ง€ ์•Š์•˜๋‹ค. 2) Wnt ๊ธธํ•ญ๋ฌผ์งˆ๊ณ„์˜ ๋‹จ์ผ ์œ ์ „์žํ˜• ๋ณ€์ด์— ๋”ฐ๋ผ์„œ๋Š” ์š”์ถ” ๋ฐ ๋Œ€ํ‡ด ๊ฒฝ๋ถ€์—์„œ์˜ ๊ณจ๋ฐ€๋„์—๋Š” ์ฐจ์ด๊ฐ€ ์—†์—ˆ๋‹ค. 3) SFRP4 ์œ ์ „์ž๋‚ด c.958 C>A ๋‹คํ˜•์„ฑ๊ณผ c.1019G>A ๋‹คํ˜•์„ฑ์–‘์ƒ์— ์˜ํ•œ ์ผ๋ฐฐ์ฒดํ˜• (haplotype) ์œ ์ „์žํ˜• AA/AA์—์„œ ์š”์ถ”์—์„œ์˜ ๊ณจ๋ฐ€๋„๊ฐ€ ๋‹ค๋ฅธ ์œ ์ „์žํ˜•์— ๋น„ํ•˜์—ฌ ๊ฐ€์žฅ ๋‚ฎ์•˜๊ณ  (p<0.05), ์ผ๋ฐฐ์ฒดํ˜• ์œ ์ „์žํ˜• AA/AA๊ฐ€ ์š”์ถ”์—์„œ์˜ ๊ณจ๋‹ค๊ณต์ฆ ์—ฌ์„ฑ์—์„œ ์ •์ƒ ๊ณจ๋ฐ€๋„ ์—ฌ์„ฑ๋ณด๋‹ค 4.37๋ฐฐ ๋” ๋นˆ๋ฒˆํ•˜๊ฒŒ ๊ด€์ฐฐ๋˜์—ˆ๋‹ค. 4) SFRP4 ์œ ์ „์ž c.958C>A ๋‹คํ˜•์„ฑ์˜ CC ์œ ์ „์žํ˜•์—์„œ ํ˜ˆ์ฒญ carboxy-terminal telopeptide of type I collagen (CTX) ๋†๋„๊ฐ€ ๋‹ค๋ฅธ ์œ ์ „์žํ˜•์— ๋น„ํ•˜์—ฌ ๋‚ฎ์•˜๊ณ  (pC ๋‹คํ˜•์„ฑ์˜ GG ์œ ์ „์žํ˜• (p<0.05)๊ณผ SFRP4 ์ผ๋ฐฐ์ฒดํ˜• ์œ ์ „์žํ˜• AA/AA(p<0.001)์—์„œ ๊ณจ ์•Œ์นผ๋ฆฌ ์ธ์‚ฐ๋ถ„ํ•ดํšจ์†Œ (bone alkaline phosphatase: BAP) ๋†๋„๊ฐ€ ๊ฐ€์žฅ ๋†’์•˜๋‹ค๋Š” ๊ฒƒ์„ ์ œ์™ธํ•˜๊ณ  Wnt ๊ธธํ•ญ๋ฌผ์งˆ๊ณ„ ๋‹ค๋ฅธ ๋‹จ์ผ ์œ ์ „์ž ๋‹คํ˜•์„ฑ์— ์˜ํ•œ ์œ ์ „์žํ˜•๊ณผ SFRP1 ์ผ๋ฐฐ์ฒดํ˜• ์œ ์ „์žํ˜• ๋ฐ SFRP4 ์ผ๋ฐฐ์ฒดํ˜• ์œ ์ „์žํ˜•์— ๋”ฐ๋ฅธ ํ˜ˆ์ฒญ ์˜ค์Šคํ…Œ์˜ค์นผ์‹ , ๋ถ€๊ฐ‘์ƒ์„ ํ˜ธ๋ฅด๋ชฌ, ์นผ์‹œํ† ๋‹Œ, ์นผ์Š˜ ๋†๋„ ์ฐจ์ด๊ฐ€ ์—†์—ˆ๋‹ค. 5) SFRP1 ์ผ๋ฐฐ์ฒดํ˜• ์ธ์ž CC๋ฅผ ๊ฐ€์ง€์ง€ ์•Š์€ ๋™ํ˜•์ ‘ํ•ฉ ์ผ๋ฐฐ์ฒดํ˜• ์œ ์ „์žํ˜•์—์„œ ๋‹ค๋ฅธ ์ผ๋ฐฐ์ฒดํ˜• ์œ ์ „์žํ˜•๋ณด๋‹ค ํ˜ˆ์ฒญ sRANKL/OPG ๋น„๊ฐ€ ๋†’๋‹ค๋Š” ๊ฒƒ์„ ์ œ์™ธํ•˜๊ณ  Wnt ๊ธธํ•ญ๋ฌผ์งˆ๊ณ„ ๋‹จ์ผ ์œ ์ „์ž ๋‹คํ˜•์„ฑ์— ์˜ํ•œ ์œ ์ „์žํ˜•๊ณผ SFRP4 ์ผ๋ฐฐ์ฒดํ˜• ์œ ์ „์žํ˜•์— ๋”ฐ๋ฅธ ํ˜ˆ์ฒญ OPG, sRANKL, ํ˜ˆ์ฒญ sRANKL/OPG ๋น„์— ์ฐจ์ด๊ฐ€ ์—†์—ˆ๋‹ค. ๊ฒฐ๋ก : ์ด์ƒ์˜ ๊ฒฐ๊ณผ๋Š” ํ•œ๊ตญ์—ฌ์„ฑ์—์„œ Wnt ๊ธธํ•ญ๋ฌผ์งˆ๊ณ„ ์ค‘ SFRP4 ์œ ์ „์ž c.958C>A์™€ c.1019G>A ๋‹คํ˜•์„ฑ์œผ๋กœ ๊ตฌ์„ฑ๋œ ์ผ๋ฐฐ์ฒดํ˜• ์œ ์ „์žํ˜•์ด ์š”์ถ”์—์„œ์˜ ๊ณจ๋ฐ€๋„์— ์˜ํ–ฅ์„ ์ฃผ๋Š” ์œ ์ „์ž ์ค‘์˜ ํ•˜๋‚˜์ผ ์ˆ˜ ์žˆ๋‹ค๋Š” ๊ฒƒ์„ ์‹œ์‚ฌํ•œ๋‹ค.์ดˆ๋ก................................................... i ๋ชฉ์ฐจ................................................. iii ๊ทธ๋ฆผ ๋ชฉ๋ก.............................................. iv ํ‘œ ๋ชฉ๋ก................................................ v ์„œ๋ก ................................................... 1 ์—ฐ๊ตฌ๋Œ€์ƒ ๋ฐ ๋ฐฉ๋ฒ•........................................ 10 ๊ฒฐ๊ณผ.................................................. 23 ๊ณ ์ฐฐ................................................. 47 ์ฐธ๊ณ ๋ฌธํ—Œ.............................................. 53 ์ดˆ๋ก (์˜๋ฌธ)............................................ 64Docto

    ํ•œ๊ตญ ์ž์—ฐํ๊ฒฝ ์—ฌ์„ฑ์—์„œ ์ธ์Š๋ฆฐ์œ ์‚ฌ ์„ฑ์žฅ์ธ์ž-I (IGF-I) ์ˆ˜์šฉ์ฒด ์œ ์ „์ž ๋‹คํ˜•์„ฑ๊ณผ ํ˜ˆ์ค‘ IGF-I ๋†๋„ ๋ฐ ๊ณจ๋ฐ€๋„์™€์˜ ์—ฐ๊ด€์„ฑ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์˜ํ•™๊ณผ ์‚ฐ๋ถ€์ธ๊ณผํ•™์ „๊ณต,2006.Maste
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