Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.
Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.
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DOI：
10.1056/nejmoa0901281
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发表时间：
2009-10-22
期刊：
影响因子：
--
通讯作者：
Ziegler SG
中科院分区：
文献类型：
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作者：
Sidransky E;Nalls MA;Aasly JO;Aharon-Peretz J;Annesi G;Barbosa ER;Bar-Shira A;Berg D;Bras J;Brice A;Chen CM;Clark LN;Condroyer C;De Marco EV;Dürr A;Eblan MJ;Fahn S;Farrer MJ;Fung HC;Gan-Or Z;Gasser T;Gershoni-Baruch R;Giladi N;Griffith A;Gurevich T;Januario C;Kropp P;Lang AE;Lee-Chen GJ;Lesage S;Marder K;Mata IF;Mirelman A;Mitsui J;Mizuta I;Nicoletti G;Oliveira C;Ottman R;Orr-Urtreger A;Pereira LV;Quattrone A;Rogaeva E;Rolfs A;Rosenbaum H;Rozenberg R;Samii A;Samaddar T;Schulte C;Sharma M;Singleton A;Spitz M;Tan EK;Tayebi N;Toda T;Troiano AR;Tsuji S;Wittstock M;Wolfsberg TG;Wu YR;Zabetian CP;Zhao Y;Ziegler SG
最近的研究表明，在帕金森病患者中，戈谢病基因葡萄糖脑苷脂酶（GBA）的突变频率增加。进行了一项国际合作研究，以确定不同种族帕金森病患者中GBA突变的频率。共有16个中心参加，其中5个来自美洲，6个来自欧洲，2个来自以色列，3个来自亚洲。每个人都接受了一个标准的DNA面板，以比较基因分型结果。采用多变量logistic回归模型和Mantel Haenszel程序分析患者和对照组的基因型和表型数据，以估计研究间的比值比（OR）。样本包括5691名患者（780名德系犹太人）和4898名对照（387名德系犹太人）。所有16个中心都可以检测到GBA突变，L444P和N370S，这两种突变在15.3%的阿什肯纳兹帕金森病患者中发现（OR = 4.95 L444P和5.62 N370S），在3.2%的非阿什肯纳兹患者中发现（OR = 9.68 L444P和3.30 N370S）。在1642名非德系犹太人受试者中进行了GBA测序，所有突变的频率为6.9%，表明有限的突变筛选错过了一半的突变等位基因。在所有研究中，任何GBA突变的存在与OR 5.43相关。在临床上，虽然表型不同，但GBA突变的受试者出现较早，并且更可能有受影响的亲属和非典型表现。从16个中心收集的数据表明，GBA突变和帕金森病之间存在很强的关联。
Recent studies indicate an increased frequency of mutations in the gene for Gaucher disease, glucocerebrosidase (GBA), among patients with Parkinson disease. An international collaborative study was conducted to ascertain the frequency of GBA mutations in ethnically diverse patients with Parkinson disease. Sixteen centers participated, including five from the Americas, six from Europe, two from Israel and three from Asia. Each received a standard DNA panel to compare genotyping results. Genotypes and phenotypic data from patients and controls were analyzed using multivariate logistic regression models and the Mantel Haenszel procedure to estimate odds ratios (ORs) across studies. The sample included 5691 patients (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews). All 16 centers could detect GBA mutations, L444P and N370S, and the two were found in 15.3% of Ashkenazi patients with Parkinson disease (ORs = 4.95 for L444P and 5.62 for N370S), and in 3.2% of non-Ashkenazi patients (ORs = 9.68 for L444P and 3.30 for N370S). GBA was sequenced in 1642 non-Ashkenazi subjects, yielding a frequency of 6.9% for all mutations, demonstrate that limited mutation screens miss half the mutant alleles. The presence of any GBA mutation was associated with an OR of 5.43 across studies. Clinically, although phenotypes varied, subjects with a GBA mutation presented earlier, and were more likely to have affected relatives and atypical manifestations. Data collected from sixteen centers demonstrate that there is a strong association between GBA mutations and Parkinson disease.