Department of Human Functional Genomics, Life Science Research Center, Mie University Department of Cell Signaling, Gifu University Graduate School of Medicine Molecular Oncology Division, National Cancer Center Research Institute Nagoya University School of Health Sciences Gifu International Institute of Biotechnology Nagoya University School of Health Sciences / Gifu International Institute of Biotechnology Gifu International Institute of Biotechnology
Institute Mexicano del Seguro Social
Archives of Medical Research
Phospholipase D2 Single nucleotide polymorphism Mutation Inactive mutant Lipid metabolism
Background. We previously showed that the 1814C→T (Thr577Ile) polymorphism of the human phospholipase D2 (PLD2) gene is associated with the prevalence of colorectal cancer, with the T allele representing a risk factor for this condition. However, we failed to detect a difference in PLD activity of cell lysates or membrane fractions between cells transfected with cDNAs encoding the Thr577 or Ile577 variants of PLD2. In the present study, we have examined the possible functional relevance of other naturally occurring polymorphisms(or mutations) of the human PLD2 gene that result in amino acid substitutions. Methods. Human embryonic kidney cells were transfected with expression vectors for each PLD2 variant and assayed for enzyme activity in vitro and in vivo. Results and Conclusions. The G→A (Gly901Asp) mutation of the human PLD2 gene was found to result in catalytic inactivation of the encoded protein.