A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci.

Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders (LPDs) show clear evidence of familial aggregation, but the inherited basis is largely unknown. To identify a susceptibility gene for CLL, we conducted a genomewide linkage analysis of 115 pedigrees, using a high-density single-nucleotide polymorphism (SNP) array containing 11,560 markers. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods.

MTHFR polymorphisms and risk of chronic lymphocytic leukemia.

Folate availability is critical for DNA integrity, required for the transfer of methyl groups in the biosynthesis of thymidilate. Reduction of 5,10-methylenetetrahydrofolate, a donor for methylating dUMP to dTMP in DNA synthesis, to 5-methyltetrahydrofolate, the primary methyl donor for methionine synthesis, is catalyzed by 5,10-methylenetetrahydrofolate reductase (MTHFR). The MTHFR polymorphisms C677T and A1298C have been shown in some studies to alter the risk of a range of different malignancies.

The P2X7 receptor gene A1513C polymorphism does not contribute to risk of familial or sporadic chronic lymphocytic leukemia.

The P2X7 receptor, a plasma membrane ATP-gated ion channel that plays a role in lymphocyte apoptosis, has been suggested to be involved in the development of chronic lymphocytic leukemia (CLL). P2X7 is polymorphic with 1513A and 1513C alleles encoding fully active and nonfunctional proteins, respectively. We evaluated the significance of the P2X7-A1513C polymorphism on CLL risk by genotyping 424 patients and 428 healthy controls.