Short reportAbsence of association between mitochondrial DNA C150T polymorphism and longevity in a Han Chinese population
Research Highlights
► No association with mtDNA C150T and longevity in Han Chinese population was found. ► No significant difference arose when stratifying samples by mtDNA haplogroup/gender. ► Previous discrepant results may be influenced by other factors.
Introduction
The relationship between the human ageing process and mitochondrial DNA (mtDNA) changes, including germ-line point mutations, somatic point mutations, and fragment deletions, has been intensely investigated over the last decade. One of the most controversial associations reported is that of human longevity with a C150T mutation on mtDNA. An early report of mtDNA haplogroup J enrichment in elderly people focused on male centenarians of northern Italy (De Benedictis et al., 1999). Subsequently, the C150T mutation defining haplogroup J2 was revealed to be the true factor associated with longevity (Niemi et al., 2003). At the same time, an analysis of nascent heavy mtDNA strands revealed a new origin of replication at position 149, substituting for that at position 151, only in cell samples carrying the C150T mutation (Zhang et al., 2003). Indeed, a number of studies with positive or negative results have been published in this area based on different populations. These paradoxical findings have motivated broader investigations for the purpose of clarifying whether the C150T mutation does contribute to human longevity and whether the association is universal to all populations or unique to particular ethnic groups. Most studies so far have focused on European populations or their derivatives, including Italian (Dato et al., 2004, De Benedictis et al., 1999, Rose et al., 2007), Finnish (Niemi et al., 2003, Niemi et al., 2005), Irish (Ross et al., 2001), Spanish (Dominguez-Garrido et al., 2009)and Ashkenazi Jewish populations (Iwata et al., 2007). In addition, populations from Japan (Niemi et al., 2005) and from Xinjiang province in China (Ren et al., 2008) have been investigated, however, the former study was limited by its small sample size and the latter was limited to Uygur subjects. To our knowledge, no previous study has investigated the putative association between the C150T mutation and longevity in a Han Chinese population, which is the largest ethnic group in the world.
We set out to explore the possible association between the mtDNA C150T polymorphism and longevity in Han Chinese subjects living in Dujiangyan city in Sichuan province, China. Dujiangyan city is renowned for having a longevous population in China, with a frequency of centenarians of more than 0.01% as indexed in the 5th National Census in China in 2000. Such a population is ideal to detect possible relations between mtDNA mutations and longevity.
Section snippets
Subjects
A total of 556 unrelated longevous individuals (202 males and 354 females aged 90–108 years) and 403 unrelated controls (204 males and 199 females aged 22–73 years) were recruited from Dujiangyan city and self-identified as being Han Chinese (Table 1). The ages of elderly subjects were authenticated by both official certification and the accounts of their offspring and other elderly neighbors. Written informed consents were obtained from all participants, and a clear explanation of the possible
Results
In this study, mtDNA C150T mutation frequency in the longevous group 124/556 (22.30%) was not significantly different compared to control group 89/403 (22.08%; p = 0.936) (Table 2). In the East Asian mtDNA phylogeny tree, haplogroups B4c1b, B4c1c, B6, D4b2b2, D5, G1a1, G1a2, G3a1, M7b and N9a have C150T as one of their definition motifs (Kong et al., 2006). In addition, three of the ten haplogroups: D5, M7b and N9a have comparatively higher frequencies than the remaining seven haplogroups in Han
Discussion
The present results indicate that the C150T polymorphism is not robustly associated with longevity in Han Chinese populations we have investigated. Pearson Chi-Square analysis revealed that the two populations in this study had similar mtDNA genetic backgrounds and showed no differences in the overall haplogroup frequencies (data not shown). A similar situation occurred in another study on longevity in a Chinese population (Cai et al., 2009). However, we still cannot rule out that other mtDNA
Acknowledgements
We are greatly indebted to the persons who participated in this research. In addition, we thank Dr. Hui Li and Dr. Yuanying Gong for their help in sample collection, and Dr. Wendy Adams's help in preparing the paper. This work was supported by the National Basic Research Program of China (No. 2007CB507405), “Light in Western China” of the Chinese Academy of Sciences, the National Natural Science Foundation of China (No. 30621092), and the Bureau of Science and Technology of Yunnan Province.
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