Transcriptional regulation of human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is essential for telomerase activity associated with telomere length. In this study, we investigated the effects of a T-1327/C polymorphism within the hTERT promoter region on the hTERT promoter activity and leukocyte telomere length in normal individuals. The promoter activity in the T-1327-sequence was significantly higher than that in the C-1327-sequence (p = 0.0004). For leukocyte telomere length, the T-1327-allele carriers had significantly longer than the T-1327-allele non-carriers (p = 0.0007). Also, there was no age-related shortening in leukocyte telomere length in the T-1327/T (p = 0.6633) and T-1327/C subjects (p = 0.1691), whereas there was clear age-related telomere shortening in the C-1327/C subjects (p = 0.0117). These findings suggest that the functional T-1327/C polymorphism of hTERT is associated with leukocyte telomere length in normal individuals. (c) 2006 Elsevier Inc. All rights reserved.