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Khảo sát tính đa hình tại SNP rs2241529 của gen DKK1 ở phụ nữ mãn kinh

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B GIO DC V O TO B Y T TRNG I HC Y H NI Vế TH LINH Khảo sát tính đa hình SNP rs2241529 gen DKK1 phụ nữ mãn kinh LUN VN THC S Y HC H NI 2016 B GIO DC V O TO B Y T TRNG I HC Y H NI Vế TH LINH Khảo sát tính đa hình SNP rs2241529 gen DKK1 phụ nữ mãn kinh Chuyờn ngnh : Ni khoa Mó s : 60720140 LUN VN THC S Y HC Ngi hng dn khoa hc: TS Trn Th Tụ Chõu H NI 2016 LI CM N hon thnh lun ny tụi luụn nhn c s giỳp tn tỡnh ca nh trng, bnh vin, gia ỡnh v bn bố Tụi xin chõn thnh cm n: Ban Giỏm hiu, B mụn Ni v Phũng o to sau i hc Trng i hc Y H Ni Ban Giỏm c, cỏc khoa phũng Bnh vin Bch Mai, ni tụi hc v cụng tỏc Vi tt c lũng yờu mn v s bit n chõn thnh sõu sc, tụi xin gi li cm n ti TS Trn Th Tụ Chõu Ngi ó hng dn tụi tn tỡnh chu ỏo, nờu mt tm gng sỏng v tinh thn hc v lm vic, ó cho tụi tỡnh thy trũ, ng nghip v dỡu dt tụi sut chng ng hc tp, nghiờn cu khoa hc Tụi xin by t s kớnh trng v lũng bit n sõu sc ti cỏc Thy Cụ hi ng ó tn tỡnh hng dn õn cn ch bo cho tụi nhng ý kin quý bỏu v phng phỏp lun, t khoa hc quỏ trỡnh nghiờn cu v hon thnh lun Tụi xin chõn thnh cm n th khoa C Xng Khp Bnh vin Bch Mai ó giỳp tụi quỏ trỡnh hc v thc hin ti Tụi xin chõn thnh cm n Vin nghiờn cu y hc inh Tiờn Hong ó cho phộp tụi tham gia ti Xỏc nh tớnh a hỡnh v s nhy cm ca cỏc gen loóng xng v góy xng trờn ngi Vit Nam mó s 106 - YS 02-2014.29 qu Nafosted ti tr, Cõu lc b im bỏo GOF d ỏn TRAC ti tr, tụi cú c hi hon thnh lun Tụi xin chõn thnh cm n B mụn Sinh Lý trng i hc Y H Ni ó giỳp tụi quỏ trỡnh hc v thc hin ti Vụ cựng bit n s chm súc, ng viờn ca cha m v nhng ngi thõn yờu ca tụi, s quan tõm giỳp v nhng tỡnh cm quý bỏu ca ngi thõn v bn bố ó dnh cho tụi H Ni, Ngy 05 /12/2016 Vừ Th Linh LI CAM OAN Tụi l Vừ Th Linh, hc viờn cao hc khúa XXIII Trng i hc Y H Ni, chuyờn ngnh Ni khoa, xin cam oan: õy l lun nhúm nghiờn cu ca chỳng tụi trc tip thc hin di s hng dn ca TS Trn Th Tụ Chõu Cụng trỡnh ny khụng trựng lp vi bt k nghiờn cu no khỏc ó c cụng b ti Vit Nam Cỏc s liu v thụng tin nghiờn cu l hon ton chớnh xỏc, trung thc v khỏch quan, ó c xỏc nhn v chp thun ca c s ni nghiờn cu Tụi xin hon ton chu trỏch nhim trc phỏp lut v nhng cam kt ny H Ni, ngy 05 thỏng 12 nm 2016 Vừ Th Linh DANH MC CH VIT TT BMI Body Mass Index (Ch s c th) CSTL Ct sng tht lng CX C xng ựi DNA Deroxyribo Nucleic Acid DXA Dual energy X-ray Absorptiometry (Hp th tia X nng lng kộp) TX u trờn xng ựi GX Góy xng KGX Khụng góy xng LX Loóng xng MX Mt xng PCR Polymease Chain Reaction (Phn ng chui trựng hp) RFLP-PCR Restriction Fragment Length Polymorphism (a hỡnh chiu di on ct gii hn) RNA Ribonucleic acid SNP Single Nucleotid Polymorphism (a hỡnh n Nucleotid) WHO World Health Organization (T chc y t th gii) MC LC T VN Chng TNG QUAN TI LIU 1.1 Tng quan v bnh loóng xng 1.1.1 nh ngha loóng xng 1.1.2 c im dch t ca loóng xng 1.1.3 Nguyờn nhõn v phõn loi loóng xng 1.1.4 Chn oỏn loóng xng 1.2 Tng quan v góy xng loóng xng 13 1.3 Tng quan v DKK1 v SNP rs2241529 18 1.3.1 V trớ v cu trỳc ca gen DKK1 v SNP rs2241529 18 1.3.2 Chc nng sinh húa ca protein DKK1 .18 1.4 Tỡnh hỡnh nghiờn cu v mi liờn quan gia gen v loóng xng, góy xng 21 1.5 Mt s k thut sinh hc phõn t ng dng phỏt hin t bin gen .23 1.5.1 K thut PCR: c Kary Mullis phỏt minh vo nm 1985 .23 1.5.2 K thut RFLP-PCR 24 1.5.3 K thut gii trỡnh t gen trc tip 26 CHNG 29 I TNG V PHNG PHP NGHIấN CU .29 2.1 a im v i tng nghiờn cu .29 2.1.1 a im nghiờn cu 29 2.1.2 Thi gian nghiờn cu 29 2.1.3 i tng nghiờn cu 29 2.2 Phng phỏp nghiờn cu 30 2.2.1 Thit k nghiờn cu .30 2.2.2 C mu 30 2.2.3 Quy trỡnh nghiờn cu 30 2.2.4 K thut phõn tớch gen DKK1 ti SNP rs2241529 34 2.2.5 Phng phỏp thu thp v x lý s liu 38 2.2.6 S quy trỡnh nghiờn cu 39 2.2.7 Vn o c ca ti 40 CHNG 41 KT QU NGHIấN CU 41 3.1 c im i tng nghiờn cu 41 3.1.1 c im chung i tng nghiờn cu .41 3.1.2 c im mt xng ca i tng nghiờn cu 42 3.1.3 c im góy xng ca nhúm loóng xng cú góy xng ct sng .43 3.2 Kt qu xỏc nh kiu gen DKK1 44 3.2.1 Kt qu tỏch chit DNA 44 3.2.2 Kt qu xỏc nh kiu gen DKK1 ti SNP rs2241529 bng phng phỏp gii trỡnh t gen 46 46 3.2.3 Kt qu xỏc nh kiu gen 47 3.3 S liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi góy xng ct sng loóng xng trờn ph n kinh 49 3.3.1 S liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi loóng xng ca i tng nghiờn cu 49 3.3.2 S liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi góy xng ca i tng nghiờn cu 50 Nhn xột: .50 Bng 3.8 cho thy khụng tỡm thy mi liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi kiu hỡnh loóng xng 50 3.3.3 S liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi mt s c im ca i tng nghiờn cu 52 CHNG 55 BN LUN 55 4.1 Bn lun v c im ca i tng nghiờn cu .55 4.2 Bn lun v kt qu phõn tớch, xỏc nh kiu gen DKK1 ta SNP rs2241529 bng k thut gii trỡnh t gen 57 4.2.1 Bn lun v s phõn b tn s alen ca gen DKK1 ti SNP rs2241529 nghiờn cu so vi tn s ngi Vit Nam v cỏc nc khỏc 58 4.2.2 Bn lun v s phõn b kiu gen DKK1 ti SNP rs2241529 nghiờn cu so vi tn s ca ngi Vit Nam v cỏc nc khỏc 59 4.3 Bn lun v s liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi góy xng ct sng loóng xng 60 4.3.1 Bn lun v s liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi loóng xng 60 4.3.2 Bn lun v s liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi góy xng ct sng loóng xng .61 Xột mi liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi kiu hỡnh loóng xng chỳng tụi cha tỡm thy mi liờn quan gia kiu gen ti SNP ny vi kiu hỡnh loóng xng Kt qu ny khụng phự hp vi nghiờn cu ca Jian yi Wang Trung Quc Tuy nhiờn c mu ca chỳng tụi nh chớnh vỡ vy tng lai cn nghiờn cu trờn c mu ln hn 61 4.3.3 Bn lun v s liờn quan gia gen DKK1 v cỏc yu t nguy c nh hng n loóng xng, góy xng ct sng loóng xng .63 4.4 im mnh, im yu ca nghiờn cu .65 KT LUN 66 Qua nghiờn cu 127 i tng l ph n kinh ngi Vit chỳng tụi rỳt mt s kt lun sau: 66 KIN NGH 67 10 Kaneki M., Hedges S J., Hosoi T et al (2001) Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk Nutrition, 17 (4), 315-321 11 Yang S., Kim D., Sohn M et al (2006) Normative study on bone mineral density in a Korean 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K et al (2009) The role of Dickkopf-1 in bone development, homeostasis, and disease Blood, 113 (3), 517-525 42 Semởnov M V., Zhang X and He X (2008) DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation Journal of Biological Chemistry, 283 (31), 21427-21432 43 Wang J., Shou J and Chen X (2000) Dickkopf-1, an inhibitor of the Wnt signaling pathway, is induced by p53 Oncogene, 19 (14), 18431848 44 Wang J., Zhou P., Liu Y et al (2016) The analysis of DKK1 polymorphisms in relation to skeletal phenotypes and bone response to alendronate treatment in Chinese postmenopausal women Pharmacogenomics, 17 (3), 209-217 45 Tian E., Zhan F., Walker R et al (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma New England Journal of Medicine, 349 (26), 2483-2494 46 Liu S., Tian W., Wang J et al (2014) Two single-nucleotide polymorphisms in the DKK1 gene are associated with developmental dysplasia of the hip in the Chinese Han female population Genetic testing and molecular biomarkers, 18 (8), 557-561 47 Lee D O., Kim H., Ku S et al (2014) Association between polymorphisms in sclerostin, dickkopfs and secreted frizzled-related protein genes and bone mineral density in postmenopausal Korean women Gynecologic and obstetric investigation, 77 (3), 186-193 48 Glantschnig H., Scott K., Hampton R et al (2011) A rate-limiting role for Dickkopf-1 in bone formation and the remediation of bone loss in mouse and primate models of postmenopausal osteoporosis by an experimental therapeutic antibody Journal of Pharmacology and Experimental Therapeutics, 338 (2), 568-578 49 Yao G.-Q., Wu J.-J., Troiano N et al (2011) Targeted overexpression of Dkk1 in osteoblasts reduces bone mass but does not impair the anabolic response to intermittent PTH treatment in mice Journal of bone and mineral metabolism, 29 (2), 141-148 50 T Thnh Vn (2010) PCR v mt s k thut y sinh hc phõn t NXB Y Hc, H Ni, 81-82 51 Waterloo S., Ahmed L A., Center J R et al (2012) Prevalence of vertebral fractures in women and men in the population-based Tromsứ Study BMC musculoskeletal disorders, 13 (1), 52 Miller D., Bryant J., Madsen E et al (1999) Evaluation and optimization of DNA extraction and purification procedures for soil and sediment samples Applied and environmental microbiology, 65 (11), 4715-4724 53 Trn Th Tụ Chõu (2002) Nghiờn cu mt s biu hin lõm sng v c xng khp v o mt xng gút bng siờu õm trờn ph n kinh H Ni, Lun thc s y hc, Trng i hc Y H Ni PH LC BNH N NGHIấN CU Xỏc nh c im cỏc im a hỡnh trờn gen DKK1 ph n kinh cú góy xng ct sng loóng xng B cõu hi sng lc 1.1 Thụng tin c bn STT Cõu hi Bỏc cú di 40 tui khụng? Bỏc ó kinh cha? Bỏc ó tng b bt ng hoc m nm lit ging hoc ngi xe y t thỏng tr lờn bao gi cha? T trc ti gi bỏc ó tng b phu thut ct d dy cha? T trc ti gi bỏc ó tng b phu thut on rut cha? (Tr ct rut tha) T trc ti gi bỏc ó tng b phu thut ct sng cha? T trc ti gi bỏc ó tng b phu thut ct b bung trng cha? T trc ti gi bỏc ó tng b phu thut ct b t cung cha? Khỏc Cú Khụng 1.2 Kt qu o mt xng v X-Quang ct sng lng v tht lng gn õy nht STT Cõu hi Kt qu o mt xng ct sng ca bỏc cú Cú Khụng bỡnh thng khụng? Kt qu o mt xng ựi ca bỏc cú bỡnh thng khụng? Kt qu chp Xquang ct sng lng v tht lng ca bỏc cú bỡnh thng khụng? 1.3 Sng lc góy xng loóng xng (Dnh cho bnh nhõn góy xng) STT Cõu hi Bỏc b góy xng ln ny cú phi tai nn giao thụng khụng? Bỏc b góy xng ln ny cú phi ngó t v trớ cao trờn chiu cao c th khụng? Hon cnh c th Cú Khụng 1.4 Bnh mn tớnh T trc ti gi ó bao gi bỏc c chn oỏn l mc cỏc bnh mn tớnh di õy cha? STT Tờn bnh Bnh suy thn i ngoi sng phõn thng xuyờn (ln hn nm) Bnh viờm gan mn tớnh Bnh x gan Bnh u nng tuyn yờn Bnh nhc nng tuyn yờn Bnh u nng tuyn giỏp Bnh nhc nng tuyn giỏp Bnh calci mỏu cao hoc cng tuyn 10 11 12 13 14 15 cn giỏp Bnh calci mỏu thp Bnh u nng tuyn thng thn Bnh nhc nng tuyn thng thn Bnh ỏi thỏo ng Bnh Cushing Bnh h thng v bnh ỏc tớnh (Lupus 16 17 18 19 20 21 22 23 24 ban , ung th.) Bnh phi tc nghn tớnh Bnh khớ ph thng Bnh x nang phi Bnh Hemophilia Bnh suy tim xung huyt Bnh leukemia Bnh tng calci huyt vụ cn Bnh thiu ht calci Bnh thiu phospho ngi trng 25 26 27 thnh Hi chng Ehlers Danlos Hi chng Menkes Kinky Hi chng Marfan Cú Khụng Nghi Ghi ng chỳ 28 29 Hi chng Klinerfelter Khỏc 1.5 Tin s dựng thuc Trong vũng thỏng qua bỏc ó bao gi dựng cỏc thuc di õy? STT Tờn thuc Ung, hớt, tiờm, bụi thuc cú dn xut Cú Khụng corticosteroid ( thỏng) Dựng thuc chng ụng heparin, Coumarin Thuc c ch dch Hoỏ tr liu Thuc iu tr suy tuyn giỏp Thuc chng co git Thuc iu tr tõm thn Cỏc cht khỏng GnRH (lupron, leuprolide acetate) Bnh ỏn nghiờn cu 2.1 Thụng tin c bn H v Tờn: Tui: S nm kinh: a ch: . in thoi: Ngh nghip: 2.2 Cỏc ch s nhõn trc Chiu cao: Chiu cao ti a: Cõn nng: BMI: 2.3 Cỏc ch s sinh tn Mch: Huyt ỏp: Nhit : Nhp th: 2.4 Tin s 2.4.1 Tin s loóng xng, góy xng * Bỏc ó bao gi b góy xng cha? Khụng S ln: V trớ: * Trong gia ỡnh bỏc cú (b, m, anh ch em rut) b loóng xng khụng? Khụng Ngi b loóng xng: * Trong gia ỡnh bỏc cú (b, m, anh ch em rut) b góy xng loóng xng khụng? Khụng Cú Ngi b góy xng: 2.4.2 Tin s bnh lý T trc n bỏc ó c chn oỏn mc bnh gỡ mn tớnh khụng? Khụng Tờn bnh: 2.4.3 Tin s dựng thuc Bỏc cú thng xuyờn (trờn thỏng) dựng mt loi thuc no khụng? Khụng Tờn thuc: 2.4.4 Tin s kinh nguyt, thai nghộn, sn ph khoa Tui bt u hnh kinh: Thi gian hnh kinh: Chu k kinh nguyờt: Kinh cú u khụng? Khụng Tui kinh: Tui tin kinh: Bỏc ó cú cha? Khụng S con: Con ln u nm bao nhiờu tui: Hin ti bỏc cú cho bỳ khụng? Khụng S ln mang thai: S ln sinh non: S ln sy thai: Bỏc ó bao gi dựng thuc trỏnh thai cha? Khụng Bỏc ó bao gi dựng hormon thay th sau kinh cha? Khụng 2.5 Cỏc ch s cn lõm sng: 2.5.1 Mt xng: Mỏy Hologic DEXA o ti CSTL v CX Region Area BMC MX (cm2) (g) (g/cm2) T-score PR (%) Z- score AM (%) L1 CSTL L2 L3 L4 Total CX Neck Troch Inter Total Wards 2.5.2 Kt qu X-Quang chn oỏn, phõn loi góy xng ct sng theo thang nh lng Phõn góy xng ct sng: 2.5.3 Cỏc xột nghim mỏu Ch s HC (g/l) HGB (g/l) Hct (l/l) BC (G/l) Mỏu lng Ca TP (mmol/l) Glucose (mmol/l) Kt qu Ch s Ure (mmol/l) Creatinin (Mmol/l) Cholesterol (mmol/l) TG/HDL/LDL (mmol/l) GOT/GPT (U/L) CRPhs H Ni, Ngy thỏng Kt qu nm 2015 PH LC KT QU CN LM SNG V PHN TCH KIU GEN CA I TNG NGHIấN CU Mó s mu LX01 LX02 LX03 LX04 LX05 LX06 LX07 LX08 LX09 LX10 LX11 LX12 LX13 LX14 LX15 LX16 LX17 LX18 LX19 LX20 LX21 LX22 LX23 LX24 LX25 LX26 LX27 LX28 LX29 LX30 LX31 LX32 LX33 LX34 LX35 LX36 LX37 H v tờn V Th Lu Nguyn Th Hoa Nguyn Thi Thờ Nguyn Th Xuõn Nguyn Th Lng Nguyn Th Thỏi Trng Th Doỏch Trn Th Minh Nguyn Th Nm o Th Hũa Nguyn Th Nhó o Th Hoa Nguyn Th Lu V Th Thỏi Ngụ Th Dựng Kim Th Ca Nguyn Th Thnh Nguyn Th Mựi Nguyn Th Nga Nguyn Th Hũa Lờ Th Khỏ Lờ Th Khụi Trn Th Den Th Quõn Nguyn Th Nhỡ T Th Ngha Thiu Th L Trn Th Vnh Th Thanh Hu Lờ TH Chõm inh Th Chanh Ngụ Th D Phm Th Dao Nguyn Th Bao Phựng Th Lan Phm Th T Lờ Th Hu Tui 53 61 65 62 51 61 61 49 47 55 67 67 62 65 51 64 51 58 60 55 68 65 60 56 68 58 63 61 68 59 70 66 49 51 54 54 76 Chn oỏn MX MX MX lõm sng LX - GX LX - KGX LX - GX KLX KLX LX - GX LX - GX LX - GX KLX LX - GX LX - GX LX - GX LX - GX KLX LX - GX LX - GX LX - GX KLX LX - GX LX - KGX LX - GX LX - GX LX - GX LX - GX LX - GX LX - GX LX - GX LX - KGX LX - GX LX - KGX LX - GX LX - KGX LX - KGX LX - KGX LX - KGX KLX KLX TX 0.732 0.716 0.704 0.75 0.978 0.905 0.562 0.749 0.67 0.711 0.979 0.82 0.782 0.794 0.983 0.764 0.76 0.935 0.68 0.853 0.95 1.013 0.875 0.77 0.682 0.637 0.336 0.71 0.943 0.914 0.977 0.727 0.639 0.935 0.768 1.032 1.088 CX 0.6 0.54 0.55 0.53 0.88 0.76 0.43 0.59 0.54 0.66 0.78 0.67 0.66 0.64 0.84 0.62 0.64 0.85 0.61 0.77 0.88 0.87 0.78 0.64 0.53 0.58 0.31 0.55 0.79 0.77 0.82 0.65 0.53 0.81 0.73 0.96 0.92 CSTL 0.914 0.885 0.621 0.828 0.956 1.147 0.492 0.795 0.71 0.68 0.94 0.712 0.722 0.681 1.024 0.679 0.709 1.104 0.611 0.913 0.885 1.012 0.889 0.653 0.775 0.689 0.521 0.663 0.889 1.045 0.884 0.592 0.623 1.068 0.703 0.895 1.093 Alen Alen A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A G A A A A A A G A A G A A G G G A G A G G G A A A G G A A A A G G A Mó s mu LX38 LX39 LX40 LX41 LX42 LX43 LX44 LX45 LX46 LX47 LX48 LX49 LX50 LX51 LX52 LX53 LX54 LX55 LX56 LX57 LX58 LX59 LX60 LX61 LX62 LX63 LX64 LX65 LX66 LX67 LX68 LX69 LX70 LX71 LX72 LX73 LX74 LX75 LX76 LX77 LX78 LX79 LX80 H v tờn Tui Ngụ Th Son Phm Th Hỏc Nguyn T.Tuyt Nhung H Th Thm H Th Sõm Trn Th Nhung Lu Th Nh Hong Th Tuyt Trn Th Lóng Bựi Th Gỏi Trn Th Tn Nguyn Th Hnh Lờ Th Cn Vừ Thi Qu Dng Th Am Lng Th Hũa Qun Th m Li Th Hi Nguyn Thi Nhiờn Phm Th Thỡn NGuyn Th Tý Nguyn Th Nhõm Nguyn Th Hon V Th Khỏnh Trn Th Hon Trn Th Thch H Th H NgUYN Th Tho NguynTh Thuõn Nguyn Th Thnh Nguyn Th B Bựi Th Chung Trn Th Xuõn Phm Th Thy ng Th Nga Lờ Th Nhiờn Nguyn Th Mai Trn Th Liờn Nguyn Th Huy Nguyn Th Sen Phm Th Hũa Phm Th Minh Nguyn Th Thnh 61 63 55 54 59 59 57 64 57 54 68 66 53 63 51 53 48 63 60 60 64 76 65 49 65 61 59 68 66 53 63 56 62 61 68 56 48 52 55 54 50 56 67 Chn oỏn MX MX MX lõm sng LX - KGX LX - KGX LX - KGX LX - KGX KLX LX - KGX LX - KGX LX - KGX KLX LX - KGX LX - GX KLX LX - KGX KLX KLX KLX KLX LX - GX LX - KGX LX - KGX LX - GX LX - GX KLX KLX KLX LX - KGX LX - KGX KLX LX - KGX KLX KLX LX - KGX LX - KGX KLX KLX LX - KGX LX - GX LX - KGX LX - KGX LX - KGX LX - KGX LX - GX LX - KGX TX 0.618 0.762 0.925 0.921 0.898 0.757 0.773 0.79 0.863 0.81 0.384 0.793 1.037 0.664 0.883 1.02 0.845 0.71 0.69 0.8 0.707 0.788 0.823 0.683 1.035 0.819 1.015 0.574 0.58 1.076 0.71 0.704 0.589 0.674 0.694 0.835 0.605 0.902 1.007 1.103 1.112 0.984 0.91 CX 0.47 0.61 0.83 0.72 0.75 0.71 0.64 0.66 0.75 0.81 0.33 0.6 0.86 0.57 0.78 0.87 0.73 0.74 0.55 0.69 0.65 0.55 0.65 0.59 0.84 0.66 0.84 0.56 0.57 0.9 0.59 0.57 0.47 0.57 0.62 0.77 0.57 0.79 0.87 0.96 0.76 0.83 CSTL 0.563 0.733 0.873 1.004 0.722 0.631 0.666 0.694 0.506 0.708 0.35 0.659 0.921 0.539 1.015 0.724 0.683 0.681 0.559 0.68 0.484 0.729 0.713 0.682 0.895 0.69 0.895 0.589 0.51 1.112 0.681 0.655 0.607 0.75 0.621 0.945 0.772 0.926 0.994 1.103 1.148 0.979 0.725 Alen Alen G A A A A A A A A A A A A A A A A A A A A A G A A A A A A A A A A A A A A A A A A A A G A G A A A A A A A G A G G G A G A G A A A G A G A G G A G A A G G A A A G A A A G A Mó s mu LX81 LX82 LX83 LX84 LX85 LX86 LX87 LX88 LX89 LX90 LX91 LX92 LX93 LX94 LX95 LX96 LX97 LX98 LX99 LX100 LX101 LX102 LX103 LX104 LX105 LX106 LX107 LX108 LX109 LX110 LX111 LX112 LX113 LX114 LX115 LX116 LX117 LX118 LX119 LX120 LX121 LX122 LX123 H v tờn Trnh Th Hon Phm Th Tõm Ngụ Th Lung Nguyn Th Hu Nguyn Th Hnh T Th Thu Phng Trn Th Hng Bựi TH Qỳy Nguyn Th Sinh Nguyn Th Minh Dng Th Khỏnh Hong Th Loan Nguyn Th Tho Trn Th Huy Nguyn Th Yờn Lý Th Tc on Th Ngc Nguyn Th ẫn Trn Th Hoa Th Ngc Nguyn Th Tuyt H Th Nhung Khoa Phm Th Ton Nguyn Th Lan Ngụ Th Ng Trn Th Li Trng Th Hin Phm Th Võn Lờ Th Duyờn Lờ Th Hõn o Th Hũa Trn Th Du Phm Th T Lng Th Tn Nguyn Th Ngc Nguyn Th An Cao Th Ngn Mai Th Kim Lờ Th Phỏn inh Th Yn Nguyn Th Thanh Nguyn Th Sen Nguyn Th Thỡn Tui 57 59 60 54 57 51 52 63 57 62 58 54 55 52 68 53 56 48 60 53 65 66 46 46 50 62 68 69 61 51 50 46 60 66 61 59 48 48 72 53 71 55 64 Chn oỏn MX MX MX lõm sng KLX LX - GX KLX LX - KGX LX - KGX LX - KGX LX - KGX LX - KGX LX - GX LX - GX LX - KGX LX - KGX KLX LX - GX KLX LX - GX LX - GX KLX LX - KGX LX - KGX LX - KGX LX - GX LX - GX KLX LX - KGX KLX KLX KLX KLX KLX LX - KGX KLX LX - GX KLX LX - GX KLX KLX KLX LX - KGX LX - GX LX - KGX KLX KLX TX 0.966 0.678 0.915 0.739 0.984 0.93 1.306 0.749 0.819 0.722 0.984 0.989 0.983 0.715 0.627 0.944 0.857 0.687 0.519 0.939 1.02 0.772 0.73 0.62 0.942 0.747 0.851 0.698 0.677 0.972 0.844 0.625 0.556 0.934 0.599 0.624 0.587 0.665 0.545 0.761 0.515 0.8 0.67 CX 0.76 0.5 0.77 0.6 0.83 0.77 1.11 0.64 0.72 0.54 0.78 0.81 0.81 0.58 0.5 0.86 0.72 0.68 0.5 0.93 0.96 0.58 0.63 0.57 0.81 0.62 0.61 0.59 0.55 0.95 0.58 0.48 0.48 0.8 0.5 0.51 0.53 0.57 0.41 0.67 0.47 0.7 0.51 CSTL 0.893 0.619 0.887 0.753 0.979 1.172 1.209 0.704 0.61 0.648 0.978 0.967 1.212 0.565 0.514 0.92 0.727 0.601 0.546 0.985 1.065 0.841 0.597 0.659 0.925 0.701 0.737 0.735 0.616 1.038 0.704 0.524 0.534 1.054 0.557 0.769 0.656 0.692 0.479 0.701 0.439 0.682 0.635 Alen Alen A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A G A G G G A G A A A A G G G A G A A A G G A A A G G G G G G G G G G G G G G G G G G G Mó s mu LX124 LX125 LX126 LX127 H v tờn Trn Th Chanh Phm Th Ngoan Nguyn Th Si Nguyn Th Thoa Tui 63 70 66 73 Chn oỏn MX MX MX lõm sng KLX LX - KGX LX - KGX KLX TX 0.787 0.46 0.662 0.682 CX 0.57 0.28 0.59 0.61 CSTL 0.665 0.62 0.694 0.562 Alen Alen A A A A G G A G ... "Kho sỏt tớnh a hỡnh ti SNP rs2241529 ca gen DKK1 ph n kinh" vi mc tiờu: Xỏc nh kiu gen DKK1 trờn ph n kinh ti SNP rs2241529 Mụ t s liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi góy xng ct...H NI 2016 B GIO DC V O TO B Y T TRNG I HC Y H NI Vế TH LINH Khảo sát tính đa hình SNP rs2241529 gen DKK1 phụ nữ mãn kinh Chuyờn ngnh : Ni khoa Mó s : 60720140 LUN VN THC S Y HC Ngi hng... kiu gen DKK1 ti SNP rs2241529 vi loóng xng 60 4.3.2 Bn lun v s liờn quan gia kiu gen DKK1 ti SNP rs2241529 vi góy xng ct sng loóng xng .61 Xột mi liờn quan gia kiu gen DKK1 ti SNP rs2241529

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