IGF-1等基因筛选举重运动员选材用分子标记的研究
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摘要
通过分析我国北方汉族普通人群及优秀举重运动员的IGF-1基因CA微卫星多态位点、ACTN3基因C1747T多态位点、CNTF基因G1357A多态位点和CKMM基因NcoI多态位点的分布特征,建立我国北方汉族优秀举重运动员DNA库,探寻举重运动员选材用分子标记。
     普通对照组206名,优秀举重运动员组94名。GeneScan分析各组IGF-1基因CA微卫星多态位点的分布特征。PCR-RFLP分析各组ACTN3基因C1747T多态位点、CNTF基因G1357A多态位点和CKMM基因NcoI多态位点的分布特征。组间比较采用x 2检验,显著性水平分别为:0.01、0.05和0.1。
     IGF-1基因CA微卫星多态位点在运动员组中基因型频率为:LL:40%、LS:45%和SS:15%,对照组基因型频率为LL:10%、LS:58%和SS:32%。优秀举重运动员携带LL基因型和L等位基因者显著多于普通对照组(p<0.001)。ACTN3基因C1747T多态位点在运动员组的基因型频率为CC:47%、TC:38%和TT:15%,对照组基因型频率为CC:31%、TC:51%和TT:18%。优秀举重运动员携带CC基因型和C等位基因者显著多于普通对照组(p<0.05)。CNTF基因G1357A多态位点在运动员组中基因型频率为GG:82%、GA:15%和AA:3%,对照组基因型频率为GG:71%、GA:27%和AA:2%。优秀举重运动员携带GG基因型者临界显著多于普通对照组,女性运动员携带GG基因型者显著多于女性普通人群对照组。一CKMM基因NcoI多态位点在运动员组的基因型频率为GG:3%、GA:30%和从:67%,对照组基因型频率为GG:2%、GA:23%和AA:75%。优秀举重运动员组的基因型分布与普通人群对照组的基因型分布没有显著性差异。IGF-1基因CA微卫星多态位点LL基因型、ACTN3基因C1747T多态位点CC基因型可以作为我国北方汉族优秀举重运动员选材用分子标记;CNTF基因G1357A多态位点GG基因型有作为我国北方汉族优秀举重运动员(尤其是女性举重运动员)选材标记的可能,需加大样本验证。CKMM基因NcoI多态位点不能作为我国北方汉族优秀举重运动员的选材标记。
The purpose of this study is to create the data base of DNA from Chinese weightlifting athletes, and to filter the genetic mark for Chinese weightlifting athlete selection through analyzing the STR CA in IGF-1 gene, the SNP C1747T in ACTN3 gene, the SNP G1357A in CNTF gene, and the SNP NcoI in CKMM gene.
     Method:The athlete group comprised 94 outstanding weight-lifting athletes (male:n=36; female:n=58), while the control group consisted of 206 healthy unrelated college students (118 males and 88 females). The distribution of genotype was got through Genescan and PCR-RFLP. The Hardy-Weinberg equilibrium is tested through X 2 test. Genotype and allele frequencies were compared between the athletes and the controls by X 2 test using SPSS software for Windows 13.0 package. P values of <0.05 were considered as a significant difference, of <0.01 were considered as a more significant difference, and of <0.1 with>0.05 were considered as a trend of significant difference.
     Result:The frequencies of the IGF-1 LL genotype (40 vs.10%; p<0.01) and L allele (63 vs.39%; p<0.01) were significantly higher in weightlifting athletes compared to controls. The frequencies of the ACTN3 CC genotype (47 vs.31%; p=0.031; p<0.05) and C allele (66 vs.56%; p=0.022; p<0.05) were significantly higher in weightlifting athletes compared to controls. The frequencies of CNTF each genotype in weightlifting athletes are:GG:82%; GA:15%; AA:3%. The frequencies of CKMM each genotype in weightlifting athletes are:GG:3%; GA:30%; AA:67%. There is no significantly difference between the weightlifting athletes and the controls of either the CNTF SNP G1357A or the CKMM SNP Ncol, while the frequency of the CNTF GG genotype is nearly significantly higher in weightlifting athletes compared to controls. The frequency of the CNTF GG genotype is significantly higher in female weightlifting athletes compared to female controls. genotype CC of the SNP C1747T in ACTN3 gene could be the genetic marks for Chinese weightlifting athlete selection. It is possible that the genotype GG of SNP G1357A in CNTF gene be the genetic marks for Chinese weightlifting athlete selection, especially female athletes, which need to be proving in the future. The SNP NcoI in CKMM could not be the genetic marks for Chinese weightlifting athlete selection.
引文
[1]桂来堂,马永红,彭根萍,等.论各种运动素质在竞技举重中的作用[J].山西体育科技,2007,27(3):11-13
    [2]杨永亮,郑伟.青少年男子举重运动员形态、机能、素质指标的选材研究[J].中国体育科技,1999,35(6):21-23
    [3]常芸,何子红.运动能力相关基因研究进展[J].中国运动医学杂志,2002,21(2):173-178
    [4]Reed T, Babsitz R, Selby J, et al. Genetic influences and grip strength norms in the NHLBI twin study males aged 50-69. Ann Hum Biol,1991,18:425-432
    [5]Thomis MA, Beunen GP, Maes HH, et al. Strength training:importance of genetic factors. Med Sci Sports Exerc,1998,30:724-731
    [6]Tiainen K, Sipila S, Alen M,et al. Heritability of maximal isometric muscle strength in older female twins. J Appl Physiol 2004,96:173-180
    [7]Calvo M, Rodas G, Vallejo M, et al. Heritability of explosive power and anaerobic capacity in humans. Eur J Appl Physiol,2002,86:218-225
    [8]Forbes GB, Sauer EP, and Weitkamp LR. Lean body mass in twins. Metabolism,1995,44: 1442-1446
    [9]Nguyen TV, Howard GM, Kelly PJ, et al. Bone mass, lean mass and fat mass:same genes or same environments? Am J Epidemiol,1998,147:3-16
    [10]Seeman E, Hopper JL, Young NR, et al. Do genetic factors explain associations between muscle strength, lean mass, and bone density? A twin study.Am J Physiol Endocrinol Metab, 1996,270:E320-E327
    [11]Thomis MA, Vlietinck RF,Maes HH, et al. Predictive power of individual genetic and environmental factor scores. M n Res,2000,3(2):99-108
    [12]Rinderknecht E, Humbel R.E. Amino-terminal sequences of two polypeptides from human serum with nonsuppressible insulin-like and cell-growth-promoting activities:Evidence for structural homology with insulin B chain, Proc. Natl Acud. Sci. USA,1976,73,2365-2369.
    [13]Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins:Biological actions. Endocr Rev,1995,16:3-34
    [14]Collett-Solberg PF&Cohen P. Genetics, chemistry, and function of the IGF/IGFBP system. Endocrine,2000,12:121-136
    [15]Liu JP, Baker J, Perkins AS, et al. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igflr). Cell,1993 75:59-72
    [16]Yang S, Alnaqeeb M, Simpson H & Goldspink G. Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch. J Muscle Res Cell Motil,1996, 17:487-495
    [17]Chakravarthy MV, Abraha TW, Schwartz RJ,et al. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3-kinase/Akt signaling pathway. J Biol Chem,2000,275:35942-35952
    [18]Barton-Davis ER, Shoturma DI, Musaro A, et al. Viral mediated expression of insulin-like growth factorI blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci U S A, 1998,95:15603-15607.
    [19]Musaro A, McCullagh K, Paul A, et al. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet,2001,27:195-200.
    [20]Hill M & Goldspink G Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage. J Physiol,2003,549:409-418
    [21]Hill M, Wernig A & Goldspink G. Muscle satellite (stem) cell activation during local tissue injury and repair. J Anat,2003,203:89-99.
    [22]Bryon R. McKay, Ciara E. O'Reilly, Stuart M. Phillips. Co-expression of IGF-1 family members with myogenic regulatory factors following acute damaging muscle-lengthening contractions in humans J Physiol,2008,586.22:5549-5560
    [23]Bamman MM, Shipp JR, Jiang J, et al. Mechanical load increases muscle IGF-I and androgen receptor Mrna concentrations in humans. Am J Physiol Endocrinol Metab,2001, 280:E383-390.
    [24]M. Hameed, R. W. Orrell, M. Cobbold G. et al. Expression of IGF-I splice variants in young and old human skeletal muscle after high resistance exercise.The Journal of Physiology,2003, 547.
    [25]Fiatarone Singh MA, Ding W, Manfredi TJ,et al. Insulin-like growth factor I in skeletal muscle after weight-lifting exercisein frail elders. Am J Physiol Endocrinol Metab,1999,277: E135-E143
    [26]Macrthur DG, North KN. A gene for speed? The evolution and function of a-actinin-3. Bioessays,2004,26(7):786-795.
    [27]Niemi AK, Majamaa K. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur J Hum Genet,2005,13(8):965-969.
    [28]North KN, Yang N, Wattanasirichaigoon D, et al. A common nonsense mutation results in alpha-actinin-3 deficiency in the general population. Nat Genet,1999,21(4):353-354.
    [29]Michelle A. Mills, Nan Yang, Ron P. Weinberger, et al. Differential expression of the actin-binding proteins,a-actinin-2and-3, in different species:implications for the evolution of functional redundancy. Hum Mol Genet,2001,10(13):1335-1346.
    [30]Rankinen T, Perusse L, Raurama R, et al. The human gene map for performance and health-related fitness phenotypes:the 2001 update. Med Sci Sports Exerc,2002,34:1219-1233
    [31]Lain A, Andrew L, Forrest F, et al. Sequence and structure organization of the human gene encoding ciliary neu-rotrephic factor.Gene,1991,102:271-276.
    [32]Ip NY, McClain J, et al. The alpha component of the CNTF receptor is required for signaling and defines potential CNTF targets in the adult and during development. Neuron 1993,10: 89-102,
    [33]Forger NG, Roberts SL, Wong V et al. Ciliary neurotrophic factor maintains motoneurons and their target muscles in developing rats. J Neurosci,1993,13:4720-4726
    [34]Yao M, Moir MS, Wang MZ, et al. Peripheral nerve regeneration in CNTF knockout mice. Laryngoscope,1999,109:1263-1268
    [35]Sendtner M, Kreutzberg GW, Thoenen Hciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature,1990,345:440-441
    [36]Oppenheim RW, Prevette D, Qin-Wei Y, et al. Control of embryonic motoneuron survival in vivo by ciliary neurotrophic factor. Science,1991,251:1616-1618.
    [37]Sendtner M, Carroll P, Holtmann B, et al. Ciliary neurotrophic factor. J Neurobiol,1994.25: 1436-1453
    [38]Sendtner M, Go'tz R, Holtmann B, et al. ciliary neurotrophic factor is a lesion factor for axotomized motoneurons in adult mice. J Neurosci.1997.17:6999-7006
    [39]王佩 马力宏等CNTF及其基因多态性的研究进展中国运动医学杂志2003,第22卷第2期
    [40]Forger NG, Roberts SL, Wong V, et al. Ciliary neurotrophic factor maintains motoneurons and their target muscles in developing rats. J Neurosci,1993.13:4720-4726
    [41]Mousavi K, Miranda W, Parry DJ. Neurotrophic factors enhance the survival of muscle fibers in EDL, but not SOL, after neonatal nerve injury. Am J Physiol Cell Physiol,2002.283: C950-C959
    [42]Friedman B, Scherer SS, Rudge JS, et al.Regulation of CNTF expression in myelin-related Schwann cells in vivo. Neuron,1992,9:295-305.
    [43]Helgren ME, Squinto SP, Davis HL, et al.Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell,1994,76:493-504.
    [44]Guillet C, Auguste P, Mayo W, et al. Ciliary neurotrophic factor is a regulator of muscular strength in aging. J Neurosci,1999.19:1257-1262
    [45]Sendtner M, Schmalbruch H, Stockli KA,et al. Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature,1992, 358:502-504
    [46]Masu Y, Wolf E, Holtmann B, et al. Disruption of the CNTF gene results in motor neuron degeneration. Nature,1993,365:27-32.
    [47]McLennan AJ, Gaskin AA, Lado DC. CNTF receptor alpha Mrna expression in rodent cell lines and developing rat. Mol Brain Res,1994,25:251-256.
    [48]Saks VA. Rosenshtraukh LV. Smirnov VN. et al. Role of creatine phospliokinase in cellular function and metabolism. Can J Physiol Pharmacol 1978:56 (5):691-706
    [49]Turner DC, Wallimann T, and Eppenberger HM. A protein that binds specifically to the M-line of skeletal muscle is identified as the muscle form of creatine kinase. Proc Natl Acad Sci USA 1973; 70:702-705
    [50]Korge P.CamphcIl KB. Local ATP regeneration is important for sarcoplasmic rcticulum Ca2+-puinp function. Am J Physiol 1994:267:C357-C366
    [51]Rossi A M, Eppenberger H M, Volpe P, Cotrufor R, and Wallimann T. Muscle-type MM creatine kinase is specifically bound to sarcoplasmic reticulum and can support Ca2+uptake and regulate local ATP/ADP ratios. Biol Cheln,1990,265:5258-5266.
    [52]Yamashita, K. and T. Yoshioka. Profiles of creatine kinase isoenzyme compositions in single muscle fibers of different types. J. Muscle Res. Cell. Motil.,1991.12:37-44
    [53]Van Deursen, J, Heerschap A, and Oerlemans F. Skeletal muscles of mice deficient in M-creatine kinase lack burst activity. Cell 1993; 74:621-631
    [54]VAN Deursen J, Ruitenbeek W, Heerschap A et al. Creatine kinase in muscle energy metabolism:a study of mouse mutants with graded reduction in CK expression.Proc Natl Acad Sci USA 1994;91:9091-5
    [55]Yvon C. Chaghon, Treva Rice, Louis Perusse, et al. Genomic scan for genes affecting body composition before and after training Cancasians from HERITAGE.J Appl Physiol,2001,90: 1777-1787
    [56]Witte S, Rogers J, and Bilezikian JP. Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene:implications for genetic studies of bone mineral density. J Clin Endocrinol Metab,1998.83:2286-2290
    [57]Ingrid Rietveld, Joop A M J L Janssenl, Albert Hofman, et al. A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels European Journal of Endocrinology,2003,148171-175
    [58]Kim JG, Roh KR, and Lee JY. The relationship among serum insulinlike growth factor-I, insulin-like growth factor-I gene polymorphism, and bone mineral density in postmenopausal women in Korea. Am J Obstet Gynecol,2002.186:345-350
    [59]Missmer SA, Haiman CA, Hunter DJ, et al. A sequence repeat in the insulin-like growth factor-1 gene and risk of breast cancer. Int J Cancer,2002.100:332-336
    [60]Vaessen N, Heutink P, Janssen JA, et al. A polymorphism in the gene for IGF-I:functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes,2001.50:637-642
    [61]Matthew C. Kostek, Matthew J. Delmonico. et al. Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults J Appl Physiol,2005, 98:2147-2154
    [62]Brian D. Hand, Matthew C. Kostek, Robert E. Influence of promoter region variants of insulin-like growth factor pathway genes on the strength-training response of muscle phenotypes in older adults J Appl Physiol,2007.103:1678-1687
    [63]Suminaga R, Matsuo M, Takeshima Y, et al. Nonsense mutation of the alpha-actinin-3 gene is not associated with dystrophinopathy. Am J Med Genet,2000,92(1):77-78.
    [64]Yang N, Daniel G, Macarthur, et al. ACTN3 genotype is associated with human elite athletic performance. Am. J. Hum. Genet,2003,73(3):627-631.
    [65]Anastasiya M, Druzhevskaya.Iidus I, Ahmetov.Irina V, et al. Association of the ACTN3 R577X polymorphism with power athlete status in Russians. Eur J Appl Physiol,2008, 103(6):631-634.
    [66]黄昌林,尚旭亚.ACTN3、ADRA2A、睫状神经营养因子基因多态性与士兵速度、耐力、力量素质的相关性[J].中国组织工程研究与临床康复,2008,12(37):1236-1237
    [67]Takahashi R, Yokoji H, Misawa H, et al. A null mutation in the human CNTF gene is not causally related to neurological diseases. Nat Genet,1994.7:79-84
    [68]Roth SM, Schrager MA, Ferrell RE, et al. CNTF genotype is associated with muscular strength and quality in humans across the adult age span. J Appl Physiol,2001.90:1205-1210
    [69]Kelsey, Bethany K.; Seip, Rick FACSM; Angelopoulos, et al.The CNTF G1357A Polymorphism and Gender Alter the Muscle Strength Response to Resistance Training.Medicine & Science in Sports&Exercise,2007,39:5
    [70]Gunther De Mars, An Windelinckx, Gaston Beunen, et al. Polymorphisms in the CNTF and CNTF receptor genes are associated with muscle strength in men and women J Appl Physiol, 2007.102:1824-1831
    [71]Arking DE, Fallin DM, Fried LP,et al. Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women. J Am Geriatr Soc,2006.54:823-826
    [72]Sean Walsh, Bethany K. Kelsey, Theodore J. Angelopoulos, et al. CNTF1357G→A polymorphism and the muscle strength response to resistance training. J Appl Physiol,2009, 107:1235-1240
    [73]Bouchard C, Rankinen T, Chagnon YC, et al. Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study. J AppI Physiol 2000; 88:551-9
    [74]Rivera.M.A.,Perusse.J.A.Simoneau.J.Gagnon,F.T. et al.Linkage between a muscle-specific CK gene marker and VO2max in the HERITAGE Family Study. Med.Sci.Sports Exerc.1999, 31:698-701.
    [75]Rivera, France T,et al.Muscle-specific creatine kinase gene polymorphism and VO2max in the Heritage family study.Med.Sci.Sports Exerc.1997,29(10):1311-1317.
    [76]周多奇,胡扬,刘刚等,耐力训练效果与CKMM基因A/G多态性的关联研究,体育科学,2006,26(7):36-39
    [77]Rivera M.A.,Dionne F.T.,Wolfarth B.et al.Muscle-specific creatine Kinase gene polymorphisms in elite endurance athletes and sedentary controls.Med.Sci.Sports Exerc.1997,29(11):1444-1447
    [78]Byung Yong Kang et al.Muscle Specific Creatine Kinase Gene Polymorphisms in Korean Elite Athletes.J.Toxicol.Pub.Health.2003,19(2):115-121.
    [79]Robert S., Cristina M., Barreda M.,et al.Association Between CKMM Genotype and EndurancePerformance Level in Hispanic Marathon Runners.Med.Sci.Sports Exerc.2004,36(5)Supplement:S260.
    [80]Yamashita, K.and T.Yoshioka.Profiles of creatine kinase isoenzyme compositions in single musclefibers of different types.J.Muscle Res.Cell.Motil,1991.12:37-44
    [81]Harrela M, Koistinen H, Kaprio J, et al. Genetic and environmental components of interindividual variation in circulating levels of IGF-1, IGF-2, IGFBP-1, and IGFBP-3. J Clin Invest,1996.98(11):2612-2615
    [82]Hong Y, Pedersen N, Brismar K, et al. Quantitative genetic analyses of insulin-like growth factor I, IGF-binding protein-1, and insulin levels in middle-aged and elderly twins. J Clin Endocrinol Metab.1996.81(5):1791-1797
    [83]Roth SM, Walsh S, Liu D, et al. The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes. Eur J Hum Genet,2008,16(3):391-394.
    [84]Barbara Vincent, Katrien D Bock, Monique Ramaekers, et al. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics,2007,32(1):58-63.
    [85]C Santiago, M Gonzalez-Freire, L Serratosa, et al. ACTN3 genotype in professional soccer players. Br. J. Sports Med,2008,42(1):71-73.
    [86]Norman B, Esbjornsson M, Rundgvist H, et al. Strength, power, fiber types, and Mrna expression in trained men and women with different ACTN3 R577X genotypes. J Appl Physiol, 2009,106(3):959-965.
    [87]DeLellis K, Ingles S, Kolonel L, McKean-Cowdin R, Henderson B,Stanczyk F, and Probst-Hensch NM. IGF1 genotype, mean plasma level and breast cancer risk in the Hawaii/Los Angeles multiethnic cohort. Br J Cancer,2003.88:277-282
    [88]Rosen CJ, Donahue LR, Hunter SJ. Insulin-like growth factors and bone:the osteoporosis connection. Proc Soc Exp Biol Med,1994.206:83-102.
    [89]Mohan S, Baylink D. Autocrine and paracrine aspects of bone metabolism.Growth Genet Horm.1990,6:1-9
    [90]Rosen CJ, Kurland ES, Vereault D, et al. Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene:implications for genetic studies of bone mineral density. J Clin Endocrinol Metab 1998.83:2286-2290,
    [91]Roth SM, Walsh S, Liu D, et al. The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes. Eur J Hum Genet,2008,16(3):391-394.
    [92]C Santiago, M G, L Serratosa, et al. ACTN3 genotype in professional soccer players[J]. Br. J. Sports Med,2008,42(1):71-73.
    [93]Barbara Vincent, Katrien D B, Monique Ramaekers, et al. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics,2007,32(1):58-63.
    [94]Lucia A, Olivan J, Gomez-Gallego F, et al. Citius and longius(faster and longer) with no alpha-actinin-3 in skeletal muscles?. Br J Sports Med,2007,41(9):616-617.
    [95]Yang N, Macarthur DG, Wolde B, et al. The ACTN3 R577X polymorphism in East and West African athletes. Med Sci Sports Exerc,2007,39(11):1985-1988.
    [96]Priscilla M. Clarkson, Joseph M. D, Heather G-D, et al. ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol 99(1): 154-163.
    [97]Delmonico MJ, Kostek MC, Doldo NA, et al. Alpha-actinin-3 (ACTN3) R577X polymorphism in influences knee extensor peak power response to strength training in older men and women. J Gerontol A Biol Sci Med Sci,2007,62(2):206-212.
    [98]Conwit RA, Ling S, Roth S, Stashuk D, Hurley B, Ferrell R, Metter EJ. The relationship between ciliary neurotrophic factor (CNTF) genotype and motor unit physiology:preliminary studies. BMC Physiol 2005.5:15,
    [99]Wilson IA,Brindle KM,Fulton AM.Differential localization of the Mrna of the M and B isofornis of creatine kinase in myohlasts.Biochcm J 1995;308:599-605

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