Identification and functional characterization of novel telomerase variant alleles in Japanese patients with bone-marrow failure syndromes.

As the incidence of bone-marrow failure syndromes (BMFS) is 2-3x higher in East Asia than in the West, we examined peripheral blood or marrow cells of 100 Japanese patients for possible pathogenic mutations in the two main components of the telomere-synthesizing enzyme telomerase (hTERC RNA and hTERT protein) that have recently been implicated in the disease pathogenesis. We analyzed samples collected from 34 patients with acquired aplastic anemia (AA), 66 patients with myelodysplastic syndromes (MDS) and 120 healthy controls. In addition to two polymorphic germ-line sequence changes (n-771A/G and n-714 C insertion) in the promoter region of hTERC and eleven hTERT polymorphisms that were identified in both patients and healthy individuals, we found a novel germ-line C323T mutation in the hTERC RNA in an MDS patient only. This heterozygous C323T mutation abolished telomerase enzymatic activity and functioned in a haploinsufficiency manner to modulate telomerase activity in cells. In summary, this study reports a novel telomerase natural variant that abolishes telomerase function, which may lead to telomere shortening and marrow hypocellularity in patients with BMFS. This study also highlights the rarity of genetic alterations in BMFS patients in Japan, which suggests that other factors may play a more prominent role in the disease pathogenesis in East Asia.

SUPPLEMENT INTAKE IN FEMALE UNIVERSITY LONG-DISTANCE RUNNERS / 体力科学

Recently, supplements for athletes are being increasingly used. To clarify the current status of supplement intake, we conducted a survey in female university long-distance runners.<BR>An anonymous questionnaire survey was conducted in runners who participated in the 18th Japan Inter-University Women's EKIDEN Championship, We investigated 99 respondents.<BR>The survey showed that 86 runners (87%) took supplements. Iron was most frequently taken (68 runners, 69%) . The common purpose was to reduce fatigue (amino acids, vitamin C) and prevent ane mia (iron) . However, some supplements were taken after their effects were realized, while others were taken without an effect. In some cases, the purpose was not consistent with the effects. Most runners (73%) purchased supplements in shops stores. Fifty percent of them took supplements for supplementation of nutrients deficient in diets. More than 50% of the runners obtained information on nutrition from their coaches.<BR>Furthermore, most runners began to take supplements when they were senior (55 runners, 56%) or junior (31 runners, 31%) high school students. About 70% of them have taken iron. In the highest percentage of them, their coaches recommended the use of supplements.<BR>The results of this survey showed that most female university long-distance runners took supplements, and that a high proportion of them began to take them when they were senior or junior high school students, suggesting the widespread use of supplements among young athletes. In addition, their instructors markedly influenced the runner's nutritional outlook, by being the source of information on nutrition.