6533b85dfe1ef96bd12bee7c
RESEARCH PRODUCT
A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome
S. RasiV. SpinaA. BruscagginT. VaisittiC. TripodoFrancesco ForconiL. D. PaoliM. FangazioE. SozziE. CenciniL. LaurentiR. MarascaC. ViscoZ. Y. Xu MonetteV. GatteiK. H. YoungF. MalavasiS. DeaglioG. GaidanoD. Rossisubject
MaleAged; Amino Acid Sequence; Animals; Disease Progression; Epidemiologic Methods; Female; Genetic Predisposition to Disease; Genotype; Humans; LDL-Receptor Related Proteins; Leukemia Lymphocytic Chronic B-Cell; Lymphoma; Male; Middle Aged; Molecular Sequence Data; Neoplasm Proteins; Polymorphism Single Nucleotide; Prognosis; Sequence Alignment; SyndromeGenotypeLymphomaMolecular Sequence DataLRP4genetics/metabolismRichter syndrome; chronic lymphocytic leukemia; LRP4 genePolymorphism Single NucleotideAnimalsHumansGenetic Predisposition to DiseaseAmino Acid SequenceChronicPolymorphismLDL-Receptor Related ProteinsAgedLeukemiaLRP4 geneB-CellSingle NucleotideSyndromeMiddle AgedPrognosisRichter syndrome.Leukemia Lymphocytic Chronic B-Cellsingle nucleotide polimorphismLymphocyticdiffuse large B cell lymphomaNeoplasm ProteinsAged Amino Acid Sequence Animals Disease Progression Epidemiologic Methods Female Genetic Predisposition to Disease Genotype Humans LDL-Receptor Related Proteins; genetics/metabolism Leukemia; Lymphocytic; Chronic; B-Cell; genetics/metabolism Lymphoma; genetics/metabolism Male Middle Aged Molecular Sequence Data Neoplasm Proteins; genetics/metabolism Polymorphism; Single Nucleotide Prognosis Sequence Alignment SyndromeSettore MED/15 - MALATTIE DEL SANGUERichter syndrome; chronic lymphocytic leukaemia; diffuse large B cell lymphoma; single nucleotide polimorphism; LRP4Disease Progressionchronic lymphocytic leukemiaFemaleRichter syndromeEpidemiologic MethodsSequence Alignmentchronic lymphocytic leukaemiadescription
Richter syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma. Risk factors of CLL transformation to RS are only partly known. We explored the role of the host genetic background as a risk factor for RS occurrence. Forty-five single nucleotide polimorphisms (SNPs) known to be relevant for CLL prognosis were genotyped in a consecutive cohort of 331 CLL, of which 21 had transformed to RS. After correcting for multiple testing and adjusting for previously reported RS risk factors, the LRP4 rs2306029 TT variant genotype was the sole SNP independently associated with a higher risk of RS transformation (Hazard Ratio: 4·17; P = 0·001; q = 0·047). The enrichment of LRP4 TT genotype in RS was confirmed in an independent series (n = 44) used for validation purposes. The LRP4 protein was expressed in CLL (n =66). Bioinformatic analysis scored LRP4 rs2306029 as a variant with possible deleterious and damaging variant of LRP4. LRP4 genotyping may help the recognition of patients with increased risk of RS at the time of CLL diagnosis.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-12-03 |