Phosphodiesterase 7B gene promoter polymorphism in patients with chronic lymphocytic leukemia.

We have found that B‐cell chronic lymphocytic leukemia (CLL) have a several‐fold increase in the mRNA of phosphodiesterase 7B (PDE7B), which catalyzes cAMP hydroysis. In order to assess the molecular basis for this increase, we tested for the presence of single nucleotide polymorphisms (SNPs) in the promoter and coding regions of the gene (chromosome 6q23‐q24). We thus undertook SNP discovery and expression using DNA isolated from peripheral blood mononuclear cells of 100 control subjects and 151 CLL patients and analyzed differences by Chi square testing. We didn't identified any SNPs in coding region but one in non‐coding, −347G>A. This SNP had a similar frequency in CLL (3%) and controls (2%, P = 0.4669); however, it was found more frequently in males vs. females. A potential explanation for this gender difference is that position −347 is a putative binding site for SRY ( s ex‐determining r egion of the Y p11.3 chromosome), which encodes a transcriptional factor that initiates male sex determination and thus, may be related to the predisposition of males to CLL. Using a luciferase assay reporter, we found that −357G>A significantly lowered the promoter activity compared to wildtype (p<0.05). Thus, the presence of −357G>A SNP in the promoter region of PDE7B, although not associated with CLL, can alter promoter activity and thus may contribute to inter‐individual and gender differences in PDE7B expression and activity.