High Prevalence of the COII/tRNA^Lys Intergenic 9‐bp Deletion in Mitochondrial DNA of Taiwanese Patients with MELAS or MERRF Syndrome

Abstract

The COII/tRNA(Lys) intergenic 9-bp deletion (MIC9D) of mitochondrial DNA (mtDNA) has been established as a genetic polymorphism for Asian-Pacific populations. We investigated whether this small mtDNA deletion is co-transmitted with human diseases such as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) and myoclonic epilepsy with ragged-red fibers (MERRF) syndromes. Forty unrelated Taiwanese families, including 12 families with MERRF and A8344G mtDNA mutation and 28 families with MELAS and A3243G mutation of mtDNA, respectively, were recruited in this study. In addition, 199 healthy subjects were recruited as control. We found that the frequency of occurrence of mtDNA with the MIC9D polymorphism in healthy subjects was 21% (41/199). However, the incidence of the MIC9D polymorphism was 67% (8/12) among the probands of all the families with MERRF syndrome (P = 0.001; OR = 8) and 39% (11/28) among the probands of the families with MELAS syndrome (P = 0.038; OR = 2). This finding indicates that the frequency of occurrence of mtDNA with the MIC9D polymorphism in patients with MERRF or MELAS syndrome is higher than that of healthy subjects. The prevalence of mitochondrial encephalomyopathies in relation to the MIC9D polymorphism of mtDNA in Taiwanese population is discussed.

New evidence of a mitochondrial genetic background paradox: Impact of the J haplogroup on the A3243G mutation

“…If the Western Eurasian haplogroup J appears to be associated to the prevalence of the A3243G mutation, it is highly provable that other haplogroups from other regions of the world could be associated. In this sense, two different studies found, first, a higher frequency of the 9 bp deletion in Taiwan MELAS patients [26] and, second, an overrepresentation of the T16189C polymorphism in patients with the A3243G mutation [50] Both markers define mtDNA haplogroup B.…”

“…Several studies suggested that certain mtDNA haplogroups affected the phenotypic expression of this mutation [26,27], but Torroni et al and Deschauer et al recently concluded that European mtDNA backgrounds did not have any substantial impact [28,29], however, these studies involved only a small number of individuals or poorly-defined populations. Thus it was impossible to confirm the relationship between mutations responsible for pathological conditions and haplogroups.…”

Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

“…[ 24 ] In Taiwanese people, the intergenic 9-bp deletion can be seen in high prevalence in MELAS or MERRF patients. [ 25 ] Recently, it has been reported that even mtDNA synonymous polymorphisms, which do not result in the substitution of amino acids, experience selection pressure, and indicate functional relevance. [ 26 ] These findings suggest the possibility that the 9-bp deletion in NC region might be subtly functional.…”

Detection of 9-bp deletion in mitochondrial genome in Vietnamese patients with suspected mitochondrial encephalomyopathy

“…Zhuo et al (2010) [8] khi xác ñịnh sự liên quan giữa hiện tượng mất ñoạn 9 bp CCCCCTCTA ở các bệnh nhân ña nang buồng trứng thì thấy tỷ lệ có mất ñoạn là 23,5%, so với người khỏe mạnh thì tỷ lệ này chỉ có 7,1% và các tác giả nhận ñịnh có sự liên quan giữa mất ñoạn và bệnh ña nang buồng trứng. Theo nghiên cứu trước ñây của Ivanova et al (1999) [2] cho thấy, tỷ lệ mất ñoạn 9 bp ở vùng gen giữa COII và tRNA Lys ở người Việt Nam khỏe mạnh là 20%, còn nghiên cứu của Liu et al (2005) [3] ở A B các bệnh nhân người Đài Loan thuộc hội chứng MELAS và MERRF cho thấy tỷ lệ mất ñoạn 9 bp là 47%, trong khi ñó, tỷ lệ này ở người khỏe mạnh là 21%. Một số tác giả cho rằng có sự bất ổn ñịnh của vùng gen COII/tRNA Lys ở các bệnh nhân bị bệnh ty thể và là ñiểm nóng cho sự mất ñoạn [8].…”