Figure 3

Index for Nrf2-modulated genes in the small airway epithelium of healthy smokers. We created an Nrf2 index that ranks the expression levels of the 13 Nrf2-modulated genes significantly modulated by smoking for all 45 healthy smokers. For each gene, individuals were divided into quartiles on the basis of the level of gene expression. Each individual was assigned a quartile designation of one, two, three, or four for each of the 13 genes. To calculate the Nrf2 index, for each individual the quartile designations for the individual were averaged across all genes. (A) Cluster analysis of Nrf2-modulated genes (from left to right) for 45 healthy smokers (from top to the bottom). The number in each object represents the quartile based on the gene expression, first quartile bright green, second dark green, third dark red, fourth bright red. The mean ± SD of the Nrf2 index is presented at the right. Note that all of the healthy smokers tend to have the same quartile for all genes, with some smokers showing low expression (that is, all green bars) of the 13 genes, some smokers intermediate expression (mixed colors), and some smokers with all 13 genes showing high Nrf2 expression (that is, all red bars). (B,C) The Nrf2 index distribution for the 45 healthy smokers was compared with an index generated in the same way by using 13 “random genes” or 13 “random smoking-responsive genes” (see Supplemental Table 2). (B) Comparison of frequency distribution of smokers among index values. Shown are the indices for the 13 Nrf2-modulated genes, the 13 random genes and the 13 “random smoking-response genes.” For each, the data is grouped by index values of 1–2, 2–3, and 3–4. Note that smokers ranked by random genes or random smoking-responsive genes have indices mostly distributed between 2 and 3, but smokers ranked by the Nrf2 genes are almost evenly distributed. (C) Comparison of SDs of individual smokers of the 13 Nrf2-modulated genes, 13 random genes, and 13 random smoking-responsive genes. Data shown are mean ± standard error. Note that the Nrf2-modulated genes have significantly less variation.