Eight-year longitudinal study of whole blood gene expression profiles in individuals undergoing long-term medical follow-up.

Sakai, Yoshio; Nasti, Alessandro; Takeshita, Yumie; Okumura, Miki; Kitajima, Shinji; Honda, Masao; Wada, Takashi; Nakamura, Seiji; Takamura, Toshinari; Tamura, Takuro; Matsubara, Kenichi; Kaneko, Shuichi

Blood circulates throughout the body via the peripheral tissues, contributes to host homeostasis and maintains normal physiological functions, in addition to responding to lesions. Previously, we revealed that gene expression analysis of peripheral blood cells is a useful approach for assessing diseases such as diabetes mellitus and cancer because the altered gene expression profiles of peripheral blood cells can reflect the presence and state of diseases. However, no chronological assessment of whole gene expression profiles has been conducted. In the present study, we collected whole blood RNA from 61 individuals (average age at registration, 50 years) every 4 years for 8 years and analyzed gene expression profiles using a complementary DNA microarray to examine whether these profiles were stable or changed over time. We found that the genes with very stable expression were related mostly to immune system pathways, including antigen cell presentation and interferon-related signaling. Genes whose expression was altered over the 8-year study period were principally involved in cellular machinery pathways, including development, signal transduction, cell cycle, apoptosis, and survival. Thus, this chronological examination study showed that the gene expression profiles of whole blood can reveal unmanifested physiological changes.