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YAHYA DAHMANY Y COLS. AN. R. ACAD. NAC. FARM.

1555G mutation in the 12S rRNA gene were overrepresented in the
mitochondrial haplogroup H (28). Two alternatives could explain
this fact. In the first one, the haplogroup might increase the
penetrance of the mutation, similar to the LHON/haplogroup J
phenomenon. In the second alternative, a founder event was
proposed. The analysis of the H subhaplogroups allowed to chose
the second one as the more probable explanation (21).

Haplogroup U has also been associated to different phenotypes
(6, 29-31). Particularly interesting is its association with the MELAS
syndrome. One study showed an excess of individuals from this
haplogroup in patients with MELAS (30). However, another more
extensive study was unable to reproduce this association (32).
Interestingly, the first study was based in patients from northern
Europe and the second one from the south and we have recently
shown significant differences in the U subhaplogroup distribution
in Europe (6). In the north, subhaplogroups U defined by
polymorphisms in very well conserved positions of the cytochrome
b and therefore with a potential phenotypic effect are
overrepresented. It has been hypothesized that these genetic variants
would affect the balance between the energy and heat production
(6, 17, 18). Northern haplogroups would be biased to a higher heat
production but lower energy production efficiency. The contrary
situation would be found in Southern haplogroups. Being this true,
then our results would suggest that the Spanish population, poorer
in U subhaplogroups defined by cytb mutations, would be less
susceptible to develop MELAS syndrome, as observed in one of the
previous studies (32).

The finest characterization of the genetic background from
different populations is a necessary first step to a rational approach
in the epidemiologic association studies as previously proposed in
the Human Genome Diversity Project (33).

ACKNOWLEDGMENTS

We would like to thank S. Morales for his technical assistance.
This work was supported by the Aragon Government Consolidated
Groups (B33), the Spanish Network for Mitochondria Disorders

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