Large scale screening of the mitochondrial DNA reveals no pathogenic mutations but a haplotype associated with multiple sclerosis in Caucasians
Large scale screening of the mitochondrial DNA reveals no pathogenic mutations but a haplotype associated with multiple sclerosis in Caucasians
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大规模线粒体 DNA 筛查未发现致病性突变，但发现与白种人多发性硬化症相关的单倍型
DOI：
10.1111/j.1600-0404.1999.tb00653.x
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发表时间：
1999
影响因子：
3.5
通讯作者：
H. Alder
中科院分区：
文献类型：
--
作者：
B. Kálmán;S. Li;D. Chatterjee;D. Chatterjee;J. O'Connor;J. O'Connor;M. R. Voehl;M. Brown;H. Alder;H. Alder
我们报告了使用限制性位点多态性和单倍型分析方法对77例复发缓解型或继发进展型多发性硬化（MS）白人患者和84例白人对照进行线粒体（mt）DNA的首次大规模筛查。没有发现与MS相关的致病性mtDNA突变。然而，mtDNA单倍型K* 和J*（由单倍群K和J中mtDNA 10，394和14，798核苷酸处同时存在DdeI限制性位点定义）显示与MS相关，P值为0.001。与对照组相比，MS患者的J* 或K* 单倍型（单倍型J或K中+10，394 DdeI/+14，798 DdeI）也相对增加（均P<0.05）。分析单倍型K* 或J* 患者的临床资料时，未观察到MS的明显表型特征。除了先前在几个MS患者中的完整测序，这里提出的mtDNA的人群筛查表明，mtDNA点突变不太可能参与MS的典型形式的发病机制。然而，线粒体遗传背景（单倍型K* 和J*）可能适度有助于MS的易感性。报道的MS和Leber遗传性视神经萎缩（一种由mtDNA点突变引起的疾病，优先发生在单倍群J）之间的关联可能至少部分与这两种疾病的重叠线粒体遗传背景有关。
We report the first large‐scale screening of mitochondrial (mt) DNA in 77 Caucasian patients with relapsing‐remitting or secondary progressive form of multiple sclerosis (MS) and in 84 Caucasian controls by using the method of restriction site polymorphism and haplotype analysis. No pathogenic mtDNA mutation was found in association with MS. However, mtDNA haplotypes K* and J* defined by the simultaneous presence of DdeI restriction sites at nucleotides 10,394 and 14,798 of the mtDNA in haplogroups K and J showed association with MS at a P‐value of 0.001. A relative increase of MS patients compared to controls either with the J* or with the K* haplotype (+ 10,394DdeI/+14,798DdeI in haplogroup J or K) also was detected (each with a P<0.05). No distinct phenotypic characteristics of MS were observed when clinical data of patients with haplotypes K* or J* were analyzed. In addition to previous complete sequencing in several MS patients, the population screening of mtDNA presented here suggests that mtDNA point mutations are not likely to be involved in the pathogenesis of typical forms of MS. However, the mitochondrial genetic background (haplotype K* and J*) may moderately contribute to MS susceptibility. The reported association between MS and Leber's hereditary optic nerve atrophy, a disease caused by mtDNA point mutations preferentially occurring in haplogroup J, may be at least in part related to the overlapping mitochondrial genetic background of the two diseases.
影响因子：
4.4
作者：
SHOFFNER, JM;BROWN, MD;WALLACE, DC
通讯作者：
WALLACE, DC
DOI：
10.1016/0006-291x(92)90479-5
发表时间：
1992-09-30
影响因子：
3.1
作者：
JOHNS, DR;NEUFELD, MJ;PARK, RD
通讯作者：
PARK, RD
影响因子：
56.9
作者：
WALLACE, DC;SINGH, G;NIKOSKELAINEN, EK
通讯作者：
NIKOSKELAINEN, EK