Yong-Gang Yao · Qing-Peng Kong · Ya-Ping Zhang Mitochondrial DNA 5178A polymorphism and longevity

Received: 9 July 2002 / Accepted: 6 August 2002 / Published online: 29 August 2002 © Springer-Verlag 2002

Abstract Previous studies have shown that mitochon- drial DNA (mtDNA) 5178 adenine/cytosine (5178A) poly- morphism, which is one of the haplogroup-specific muta- tions for mtDNA haplogroup D, was apparently associ- ated with aging and longevity in humans. We genotyped the 5178A in 293 samples representing three age groups (Old, n=95; Young, n=103; and Infant, n=95) from Yunnan Province, China. The distribution frequency of the 5178A in the Old samples (16.84%) is slightly higher than in those of the Young (13.59%) and Infant (15.79%), but the frequency difference between the age groups is far from being statistically significant (P>0.05). Our results fail to support the suggestion of association between mtDNA 5178A (or haplogroup D) and longevity.

(excluding the mutations that might undergo recurrent mutations). This kind of arrangement of mtDNAs into ma- jor (and minor) haplogroups has been widely used in re- constructing the past in human beings (Torroni et al. 2000; Yao et al. 2002; Kivisild et al. 2002). The 5178A polymor- phism is one of such haplogroup-specific mutations for mtDNA haplogroup D. Our recent study of Han Chinese mtDNAs revealed that there was a general increase in the frequency of haplogroup D, namely the 5178A genotype, from southern to northern China (Yao et al. 2002). Due to the suggestion of association between 5178A and longevity, as proposed by Tanaka et al. (1998, 2000), questions may naturally arise from a phylogenetic point of view. Do mtDNA haplogroup D individuals tend to live longer? Do those populations that harbor a large number of hap- logroup D individuals have a higher life expectancy?

The mitochondrial DNA 5178 adenine/cytosine (5178A) polymorphism in the NADH dehydrogenase subunit 2 (ND2) gene has been reported to be associated with aging and longevity in the Japanese people (Tanaka et al. 1998, 2000). Recent studies also showed that this polymorphism was associated with serum lipid levels in blood (Kokaze et al. 2001), and that the 5178A genotype is prone to resist adult-onset diseases by suppressing obesity and athero- sclerosis (Tanaka et al. 2000, and references therein).

presence of mtDNA 5178A in 293 healthy individuals from Kunming, Yunnan Province, China, using PCR-re- striction fragment length polymorphism analysis as de- scribed in our recent study (Yao et al. 2002). The absence of the 5176 AluI site was designated as 5178A, while the presence of the site was designated as 5178C [note that Kokaze et al. (2001) mistook the absence of the AluI site as 5178C]. The subjects considered were placed into three groups according to their ages: (a) Old – older adults over 70 years of age, (b) Young – younger adults 24–37 years old, and (c) Infant – children 4 days to 2 years old (Table 1). The age differences between the three groups were statis- tically significant (P<0.001, two-tailed; independent sam- ples t-test).

Owing to its maternal inheritance and absence of re- combination, each mtDNA sequence could be assigned to a certain mtDNA haplogroup (a monophyletic clade in the rooted mtDNA tree) according to the mutations it har- bored. These mutations that defined a haplogroup were thus regarded as haplogroup-specific mutations and were only

Table 1 shows the distributions of mtDNA 5178A in the three age groups. The Old individuals had the highest frequency of 5178A polymorphism at 16.84%, followed by the Infant group (15.79%), whereas the Young group had the lowest frequency. Contrary to expectations (Tanaka et al. 1998), there was no increase in the frequency of the 5178A as the age increased. The differences in the 5178A frequencies between the three age groups were also not statistically significant (P>0.05; Fisher exact test). The

Y.-G. Yao · Q.-P. Kong · Y.-P. Zhang ) Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming

, China e-mail: zhangyp@public.km.yn.cn, Tel.: +

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Y.-G. Yao · Q.-P. Kong Graduate School of The Chinese Academy of Sciences,

Group n Average age Frequency of 5178A P valuea (years) (%) (a) Old 95 76.2±5.0 16.84 Old vs Young, P=0.363 (b) Young 103 30.2±3.8 13.59 Young vs Infant, P=0.429 (c) Infant 95 1.3±1.1 15.79 Old vs Infant, P=0.511

overall frequency of 5178A in the total 293 subjects (15.4%) is similar to that of the Yunnan sample in our re- cent study (Yao et al. 2002).

ples. We are also indebted to Si-Kang Gou and Si-Fang Wu for technical assistance. The work was supported by NSFC and Nat- ural Science Foundation of Yunnan Province.