SEATTLE--Some people who have a particular form of a gene that, when mutated, causes Werner's syndrome--a rare disorder characterized by rapid aging in youth--appear to have a relatively low risk of suffering a heart attack. The finding, presented here at the annual meeting of the American Association for the Advancement of Science (which publishes ScienceNOW), suggests that the blood-vessel damage that precedes a heart attack could in certain people arise from poor DNA repair.
University of Washington pathology professor George Martin and his colleagues at the Osaka University Medical School in Japan studied 347 Japanese, each with one of three versions of the Werner gene: the so-called cysteine-cysteine (CC), cysteine-arginine (CR), and arginine-arginine (RR) genotypes. (Werner's syndrome itself is caused by a mutation in any one of these three forms.) The group found that people with the CR or RR genotypes--which together occur in about 15% of the population--are nearly three times less likely to suffer a heart attack than are people with the CC genotype. The findings appear in the current issue of the American Journal of Medical Genetics.
The Werner gene codes for a helicase, an enzyme that unwinds DNA strands and is believed to play a role in DNA repair, replication, and transcription. The CR genotype produces two kinds of helicase--one with cysteine and one with arginine--while the homozygous versions produce one helicase or the other. Martin speculates that the arginine version may work better and decrease the chance of DNA damage.
With a less efficient helicase and therefore less efficient DNA repair, Martin suggests, atherosclerotic lesions could arise like tumors from mutations in single cells, besides their well-known origin from chronic inflammation from high-fat diets. "The role of DNA damage in atherosclerosis has been rather neglected," Martin says. "But this study shows it's definitely something worth looking at." So agrees George Roth of the National Institute on Aging: "It's fascinating that there is such a link, if it holds up."