• 1. 首都醫(yī)科大學宣武醫(yī)院神經(jīng)內(nèi)科,宣武醫(yī)院北京老年病研究所神經(jīng)生物學研究室,北京,1000532. 首都醫(yī)科大學流行病學衛(wèi)生統(tǒng)計中心,北京,100053;

目的 　運用Meta-分析的方法綜合評價parkin基因S/N167多態(tài)性與帕金森病(PD)發(fā)病的關系.
方法 　檢索Medline、Cochrane圖書館(英文)和中國生物醫(yī)學文獻數(shù)據(jù)庫(CBM)(中文),納入內(nèi)容涉及parkin基因S/N167多態(tài)的基因型頻率和(或)等位基因頻率的獨立病例對照研究,同時手檢并納入了我們研究組未發(fā)表的文獻.各文獻滿足研究方法相似,有綜合的統(tǒng)計指標.研究年限為1998～2003年.語種不限.排除不符合納入標準,未涉及S/N167多態(tài)基因頻率的對照研究.應用RevMan4.2軟件進行統(tǒng)計分析.
結果 　合并統(tǒng)計,總體效應檢驗未發(fā)現(xiàn)統(tǒng)計學上的差異(Z=1.57,P=0.12),但根據(jù)東西方人群進行分組分析后發(fā)現(xiàn),S/N167多態(tài)在基因型水平[OR=1.41,95%CI=(1.08,1.83),P=0.01]和等位基因水平[OR=1.25,95%CI=(1.08,1.44),P=0.01]均可能增加東方人群患PD的發(fā)病風險.加入我們研究組的未發(fā)表資料后,上述結論未改變,趨勢更明顯.而西方人群在基因型水平[OR=0.55,95%CI=(0.30,1.02),P=0.06]和等位基因水平[OR=0.55,95%CI=(0.28,1.08),P=0.08]均無統(tǒng)計學上的差異.
結論 　我們的Meta-分析結果提示,S/N167多態(tài)性可能增加了東方人群患PD的危險性,對西方人群的影響尚不確定.

引用本文： 鄒海強,陳彪,彭曉霞,馮秀麗,董秀敏. Parkin基因S/N167多態(tài)性與帕金森病發(fā)病風險的Meta-分析. 中國循證醫(yī)學雜志, 2004, 04(3): 157-163. doi: 復制

1. ［1］Chan P, Tanner CM, Zhao L, et al. Prevalence of Parkinson ’s disease in Beijing, China[J]. Neurology, 2000; 54 (Suppl 3): A348.
2. ［2］Dekker MC, Bonifati V, van Duijn CM. Parkinson’s disease:piecing together a genetic jigsaw [ J ]. Brain, 2003; 126 ( Pt 8) :1 722-1 733.
3. ［3］Lim KL, Dawson VL, Dawson TM. The genetics of Parkinson’s disease [ J ]. Curr Neurol Neurosci Rep, 2002; 2 ( 5 ):439-446.
4. ［4］Scott WK, Nance MA, Watts RL, Hubble Jp, Koller WC,Lyons K, Pahwa R, Stem MB, Colcher A, Hiner BC,Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW,Masterman D, Mastaglia F, Laing NG, Stajich JM,Slotterbeck B, Booze MW, Ribble RC, Rampersaud E,West SG, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott BL, Vance JM, Pericak-Vance MA. Complete genomic screen in Parkinson disease: evidence for multiple genes[J]. JAMA, 2001; 286(18) :2 239-2 244.
5. ［5］Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G,Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW,Agid Y, Brice A. Association between early-onset Parkinsons disease and mutations in the parkin gene[J]. N Engl J Med,2000; 342(21) :1 560-1 567.
6. ［6］Oliveira SA, Scott WK, Martin ER, Nance MA, Watts RL,Hubble Jp, Koller WC, Pahwa R, Stem MB, Hiner BC,Ondo WG, Allen FH Jr, Scott BL, Goetz CG, Small GW,Mastaglia F, Stajich JM, Zhang F, Booze MW, Winn MP,Middleton LT, Haines JL, Pericak-Vance MA, Vance JM.Parkin mutatons and susceptibility alleles in late-onset Parkinson’s disease[J]. Ann Neurol, 2003; 53(5) :624-629.
7. ［7］Hattoti N, Kitada T, Matsumine H, Asakawa S, Yamamura Y, Yoshino H, Kobayashi T, Yokochi M, Wang M,Yoritaka A, Kondo T, Kuzuhara S, Nakamura S, Shimizu N, Mizuno Y. Molecular genetic analysis of a novel parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: evidence for variable homozygous deletions in the parkin gene in affected individuals [J ]. Ann Neurol, 1998;44(6) :935-941.
8. ［8］Klein C, Schumacher K, Jacob H, Hagenah J, Kis B, Garrels J, Schwinger E, Ozelius L, Pramstaller P, Vieregge P,Kramer PL. Association Studies of Parkinson’s Disease and parkin Polymorphisms [ J ]. Annals of Neurology, 2000; 48( 1 ): 126-127.
9. ［9］Satoh JI, Kuroda Y. Association of codon 167 Ser/Asn heterozygosity in the parkin gene with sporadic Parkinson’s disease[J].Neuroreport, 1999; 10(13): 2 735-2 739.
10. ［10］Hu CJ, Sung SM, Liu HC, Lee CC, Tsai CH, ChangJG.Polymorphisms of the Parkin Gene in Sporadic Parkinson’s Disease among Chinese in Taiwan[J]. European Neurology,2000; 44(2): 90-93.
11. ［11］Wang M, Hattori N, Matsumine H, Kobayashi T, Yoshino H, Morioka A, Kitada T, Asakawa S, Minoshima S, Shimizu N, Mizuno Y. Polymorphism in the Parkin Gene in Sporadic Parkinson’s Disease[J]. Annals of Neurology, 1999; 45(5):655-658.
12. ［12］PengR, Yinru G, Yuan Q, Li T, Latsoudis H, Yuan G,Luo D, Liu X, Collier DA. Mutation screening and association analysis of the parkin gene in parkinson’s disease patients from south-west China [ J ]. European Neurology,2003; 49(2) :85-89.
13. ［13］Mata IF , Alvarez V , Garcia- Moreira V , Guisasola LM ,Ribacoba R, Salvador C, Blazquez M, Sarmiento RG, Lahoz CH, Menes BB, Garcia EC. Single-nucleotide polymorphisms in the promoter region of the PARKIN gene and Parkinson’s disease[J]. Neurosci Lett, 2002,329(2):149-152.
14. ［14］NingYP, Liu ZL, Xu YM, et al. Association study ofparkin gene S/N 167 ploy-morphism with sporadic Parkinson’s disease[J]. Chin J Med Genet. 2001; 19(6): 513-514.
15. 寧玉萍,劉焯霖,徐嚴明等.parkin基因S/N167多態(tài)性與散發(fā)性帕金森病關聯(lián)研究[J].中華醫(yī)學遺傳學雜志,2002;19(6):513-514.
16. ［15］Mellick GD, BuchananDD, HattoriN, Brookes AJ, Mizuno Y, Le Couteur DG, Silbum PA. The parkin gene S/N167polymorphism in Australian Parkinson’s disease patients and controls[J]. Parkinsonism and Related Disorders, 2001; 7(2) :89-91.
17. ［16］Oliveira SA, Scott WK, Nance MA, Watts Ri, Hubble Jp,Koller WC, Lyons KE, Pahwa R, Stem MB, Hiner BC,Jankovic J, Ondo WG, Allen FH Jr, Scott BL, Goetz CG,Small GW, Mastaglia FL, Stajich JM, Zhang F, Booze MW,Reaves JA, Middleton LT, Haines JL, Pericak-Vance MA,Vance JM, Martin ER. Association study of parkin gene polymorphisms with idiopathic Parkinson disease [ J ]. Arch Neurol, 2003 ;60(7 ) :975-980.
18. ［17］Abbas N, Lucking CB, Ricard S, Durr A, Boulfati V, De Michele G, Bouley S, Vaughan JR, Gasser T, Marconi R,Broussolle E, Brefel-Courbon C, Hathangi BS, Oostra BA,Fabrizio E, Bohme GA, Pradier L, Wood NW, Filla A,Meco G, Denefle P, Agid Y, Brice A. A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe[J]. Hum Mol Genet, 1999;8(4) :567-574.
19. ［18］Petitti DB. Meta-analysis, decision analysis and cost-effectiveness[M]. New York :Oxford University Press, 1994; 1-237.
  1. 1. ［1］Chan P, Tanner CM, Zhao L, et al. Prevalence of Parkinson ’s disease in Beijing, China[J]. Neurology, 2000; 54 (Suppl 3): A348.
  2. 2. ［2］Dekker MC, Bonifati V, van Duijn CM. Parkinson’s disease:piecing together a genetic jigsaw [ J ]. Brain, 2003; 126 ( Pt 8) :1 722-1 733.
  3. 3. ［3］Lim KL, Dawson VL, Dawson TM. The genetics of Parkinson’s disease [ J ]. Curr Neurol Neurosci Rep, 2002; 2 ( 5 ):439-446.
  4. 4. ［4］Scott WK, Nance MA, Watts RL, Hubble Jp, Koller WC,Lyons K, Pahwa R, Stem MB, Colcher A, Hiner BC,Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW,Masterman D, Mastaglia F, Laing NG, Stajich JM,Slotterbeck B, Booze MW, Ribble RC, Rampersaud E,West SG, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott BL, Vance JM, Pericak-Vance MA. Complete genomic screen in Parkinson disease: evidence for multiple genes[J]. JAMA, 2001; 286(18) :2 239-2 244.
  5. 5. ［5］Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G,Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW,Agid Y, Brice A. Association between early-onset Parkinsons disease and mutations in the parkin gene[J]. N Engl J Med,2000; 342(21) :1 560-1 567.
  6. 6. ［6］Oliveira SA, Scott WK, Martin ER, Nance MA, Watts RL,Hubble Jp, Koller WC, Pahwa R, Stem MB, Hiner BC,Ondo WG, Allen FH Jr, Scott BL, Goetz CG, Small GW,Mastaglia F, Stajich JM, Zhang F, Booze MW, Winn MP,Middleton LT, Haines JL, Pericak-Vance MA, Vance JM.Parkin mutatons and susceptibility alleles in late-onset Parkinson’s disease[J]. Ann Neurol, 2003; 53(5) :624-629.
  7. 7. ［7］Hattoti N, Kitada T, Matsumine H, Asakawa S, Yamamura Y, Yoshino H, Kobayashi T, Yokochi M, Wang M,Yoritaka A, Kondo T, Kuzuhara S, Nakamura S, Shimizu N, Mizuno Y. Molecular genetic analysis of a novel parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: evidence for variable homozygous deletions in the parkin gene in affected individuals [J ]. Ann Neurol, 1998;44(6) :935-941.
  8. 8. ［8］Klein C, Schumacher K, Jacob H, Hagenah J, Kis B, Garrels J, Schwinger E, Ozelius L, Pramstaller P, Vieregge P,Kramer PL. Association Studies of Parkinson’s Disease and parkin Polymorphisms [ J ]. Annals of Neurology, 2000; 48( 1 ): 126-127.
  9. 9. ［9］Satoh JI, Kuroda Y. Association of codon 167 Ser/Asn heterozygosity in the parkin gene with sporadic Parkinson’s disease[J].Neuroreport, 1999; 10(13): 2 735-2 739.
  10. 10. ［10］Hu CJ, Sung SM, Liu HC, Lee CC, Tsai CH, ChangJG.Polymorphisms of the Parkin Gene in Sporadic Parkinson’s Disease among Chinese in Taiwan[J]. European Neurology,2000; 44(2): 90-93.
  11. 11. ［11］Wang M, Hattori N, Matsumine H, Kobayashi T, Yoshino H, Morioka A, Kitada T, Asakawa S, Minoshima S, Shimizu N, Mizuno Y. Polymorphism in the Parkin Gene in Sporadic Parkinson’s Disease[J]. Annals of Neurology, 1999; 45(5):655-658.
  12. 12. ［12］PengR, Yinru G, Yuan Q, Li T, Latsoudis H, Yuan G,Luo D, Liu X, Collier DA. Mutation screening and association analysis of the parkin gene in parkinson’s disease patients from south-west China [ J ]. European Neurology,2003; 49(2) :85-89.
  13. 13. ［13］Mata IF , Alvarez V , Garcia- Moreira V , Guisasola LM ,Ribacoba R, Salvador C, Blazquez M, Sarmiento RG, Lahoz CH, Menes BB, Garcia EC. Single-nucleotide polymorphisms in the promoter region of the PARKIN gene and Parkinson’s disease[J]. Neurosci Lett, 2002,329(2):149-152.
  14. 14. ［14］NingYP, Liu ZL, Xu YM, et al. Association study ofparkin gene S/N 167 ploy-morphism with sporadic Parkinson’s disease[J]. Chin J Med Genet. 2001; 19(6): 513-514.
  15. 15. 寧玉萍,劉焯霖,徐嚴明等.parkin基因S/N167多態(tài)性與散發(fā)性帕金森病關聯(lián)研究[J].中華醫(yī)學遺傳學雜志,2002;19(6):513-514.
  16. 16. ［15］Mellick GD, BuchananDD, HattoriN, Brookes AJ, Mizuno Y, Le Couteur DG, Silbum PA. The parkin gene S/N167polymorphism in Australian Parkinson’s disease patients and controls[J]. Parkinsonism and Related Disorders, 2001; 7(2) :89-91.
  17. 17. ［16］Oliveira SA, Scott WK, Nance MA, Watts Ri, Hubble Jp,Koller WC, Lyons KE, Pahwa R, Stem MB, Hiner BC,Jankovic J, Ondo WG, Allen FH Jr, Scott BL, Goetz CG,Small GW, Mastaglia FL, Stajich JM, Zhang F, Booze MW,Reaves JA, Middleton LT, Haines JL, Pericak-Vance MA,Vance JM, Martin ER. Association study of parkin gene polymorphisms with idiopathic Parkinson disease [ J ]. Arch Neurol, 2003 ;60(7 ) :975-980.
  18. 18. ［17］Abbas N, Lucking CB, Ricard S, Durr A, Boulfati V, De Michele G, Bouley S, Vaughan JR, Gasser T, Marconi R,Broussolle E, Brefel-Courbon C, Hathangi BS, Oostra BA,Fabrizio E, Bohme GA, Pradier L, Wood NW, Filla A,Meco G, Denefle P, Agid Y, Brice A. A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe[J]. Hum Mol Genet, 1999;8(4) :567-574.
  19. 19. ［18］Petitti DB. Meta-analysis, decision analysis and cost-effectiveness[M]. New York :Oxford University Press, 1994; 1-237.