• 1. 首都醫(yī)科大學(xué)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(xué)研究室,北京,1000532. 首都醫(yī)科大學(xué)流行病學(xué)衛(wèi)生統(tǒng)計(jì)中心,北京,100053;

目的 　運(yùn)用Meta-分析的方法綜合評(píng)價(jià)parkin基因S/N167多態(tài)性與帕金森病(PD)發(fā)病的關(guān)系.
方法 　檢索Medline、Cochrane圖書館(英文)和中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)(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(dú)立病例對(duì)照研究,同時(shí)手檢并納入了我們研究組未發(fā)表的文獻(xiàn).各文獻(xiàn)滿足研究方法相似,有綜合的統(tǒng)計(jì)指標(biāo).研究年限為1998～2003年.語(yǔ)種不限.排除不符合納入標(biāo)準(zhǔn),未涉及S/N167多態(tài)基因頻率的對(duì)照研究.應(yīng)用RevMan4.2軟件進(jìn)行統(tǒng)計(jì)分析.
結(jié)果 　合并統(tǒng)計(jì),總體效應(yīng)檢驗(yàn)未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)上的差異(Z=1.57,P=0.12),但根據(jù)東西方人群進(jìn)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?xùn)|方人群患PD的發(fā)病風(fēng)險(xiǎn).加入我們研究組的未發(fā)表資料后,上述結(jié)論未改變,趨勢(shì)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(wú)統(tǒng)計(jì)學(xué)上的差異.
結(jié)論 　我們的Meta-分析結(jié)果提示,S/N167多態(tài)性可能增加了東方人群患PD的危險(xiǎn)性,對(duì)西方人群的影響尚不確定.

引用本文： 鄒海強(qiáng),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(fēng)險(xiǎn)的Meta-分析. 中國(guó)循證醫(yī)學(xué)雜志, 2004, 04(3): 157-163. doi: 復(fù)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(yán)明等.parkin基因S/N167多態(tài)性與散發(fā)性帕金森病關(guān)聯(lián)研究[J].中華醫(yī)學(xué)遺傳學(xué)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(yán)明等.parkin基因S/N167多態(tài)性與散發(fā)性帕金森病關(guān)聯(lián)研究[J].中華醫(yī)學(xué)遺傳學(xué)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.