454 Race and leukocyte telomere length, S. C. Hunt et al. Fig. 3 Sex- and body mass index-adjusted leukocyte telomere length (LTL) vs. age for African Americans and whites from the NHLBI Family Heart Study (FHS) and the Bogalusa Heart Study (BHS) combined. counts than did whites, no relationships were observed between these counts and LTL in African Americans and whites, independently or jointly. Figure 3 displays sex- and BMI-adjusted LTL vs. age from the combined data set of the FHS and BHS, using LTL derived from HinfI/RsaI digest. African Americans had higher LTL at nearly all ages. However, sex- and BMI-adjusted LTL became shorter with age at a steeper slope in African Americans (0.029 kb year–1) than in whites (0.020 kb year–1) (p = 0.0001). The slope of LTL vs. age did not differ by sex. Discussion The central finding of this study is that African Americans have considerably longer LTL than whites, at least up to age 80. In this study, we observed a sex effect on LTL in the NHLBI FHS, but in the BHS, the sex effect was found only in the products of the HphI/MnII. A potential explanation for the difficulty in detecting the sex effect may be the much younger age of the BHS participants. In the FHS and in previous studies that found longer LTL in women than men (Jeanclos et al., 2000; Benetos et al., 2001; Nawrot et al., 2004; Vasa-Nicotera et al., 2005; Bekaert et al., 2007), the subjects were much older than those in the BHS. LTL is equal in African American and white newborns (Okuda et al., 2002). As African Americans in their 20s already display longer LTL than their white peers, the racial gap in LTL might relate to factors that define leukocyte telomere dynamics during the formative years. These include the proliferative rates of HSCs/PCs. African Americans and other individuals of African ancestry display lower leukocyte and neutrophil counts than do whites (Haddy et al., 1999; Bain et al., 2000; Phillips et al., 2000; Mayr et al., 2007), a finding we confirmed in the BHS. The neutrophils in peripheral blood are distributed into two pools; namely, circulating cells and marginated cells that adhere to the endothelium in postcapillary venules (Athens et al., 1961). Physiological neutropenia in individuals of African ancestry is not due to increased margination of neutrophils (Athens et al., 1961; Bain et al., 2000; Phillips et al., 2000). It is therefore likely to arise from fewer replications of HSCs/PCs. The longer LTL in African Americans than in whites is consistent with this premise. Telomere length is shorter in neutrophils than in T lymphocytes in young individuals and vice versa in older individuals (Weng, 2001). For the following reasons, we suggest that in and of itself this phenomenon does not explain the racial difference in LTL: First, LTL was found to be longer in African Americans than in whites at a wide age range that encompasses most of adult life. Second, there are considerable interindividual variations in LTL at birth (Okuda et al., 2002; Akkad et al., 2006) and there- after (Jeanclos et al., 2000; Benetos et al., 2001; Gardner et al., 2005; Nawrot et al., 2005; Valdes et al., 2005; Vasa-Nicotera et al., 2005; Bekaert et al., 2007; Njajou et al., 2007). These interindividual variations in telomere length far exceed the variation in telomere length among cell types within the individual, because telomere length is synchronized (equivalent) in different tissues and cells in the fetus (Youngren et al., 1998) and the newborn (Okuda et al., 2002), and partially synchronized at any age (Butler et al., 1998; Martens et al., 1998; von Zglinicki et al., 2000; Takubo et al., 2002; Gardner et al., 2007). It follows that individuals with relatively long (or short) telomere length in one cell type have long (or short) telomere length in other cell types. Regarding telomere dynamics in leukocytes, LTL reflects birth telomere length and replicative history of HSCs/ PCs. At any given time, and for whatever reason and duration, an altered demand by a leukocyte subset on PCs to increase or diminish their divisions would ultimately impact telomere dynamics in HSCs and therefore telomere length in all leukocytes. It is unlikely therefore that the racial differences in LTL may be simply explained by a subset of leukocytes. Third, in the BHS we found no association of LTL with the numbers of either leukocytes or neutrophils (Supplementary Table S1). This is not unexpected, as LTL is a record of the replicative history of HSCs/PCs over the individual’s lifetime until sample collection, while the leukocyte and neutrophil counts reflect a ‘snapshot’ of the peripheral leukocytes at the time of sample collection. Although diminished HSC/PC replication might explain the longer LTL in African Americans than in whites during early adulthood, additional factors apparently tip the balance towards narrowing the racial gap in LTL later in life. Theoretical consid- erations suggest that telomere attrition rate in cultured cells is proportional to telomere length (op den Buijs et al., 2004), perhaps because longer telomeres are a greater target to free radicals. All other things being equal, the relatively longer LTL in adult African Americans may account in part for a higher rate of LTL shortening. In addition, African Americans exhibit increased prevalence of risk factors – not only for CV disease (whose pattern may not be the same as in whites), but also for other potentially deleterious conditions, e.g. low social status and © 2008 The Authors Journal compilation © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2008