Impact of copy number variations within the defensin locus on 8p23 and the cystathionine beta synthase gene in human sepsis and sepsis complications
Acronym: CNV
Principal Investigator: Dr. med. Christoph Sponholz
Research Area: A Risk Assessment and Sepsis Control
Project Number: A3.1
Duration: 01.04.2011 - 31.03.2013
Module: Rotational Position
The Problem
The project represents a genetic association study, focussing on two different gene loci that may affect susceptibility and outcome of severe sepsis. In addition to single nucleotide polymorphisms (SNP), Copy number variations (CNV) may reflect a hitherto underestimated molecular mechanism affecting gene expression. While in the defensin locus on chromosome 8p23 a cluster of whole genes are involved by CNV´s, the CBS gene is only partially affected by CNV represented by a variable number of tandem repeats (VNTR) at the exon15-intron15 boundary. We therefore focus our investigation on these two gene loci, that have also been shown to have impact on infectious diseases.
Results so far
CNV in human beta-defensin cluster:
N=220 patients suffering from severe sepsis/septic shock were genotyped for CNV and SNPs within the beta-defensin gene cluster. Genotypes were compared to non-septic age and gender matched patients, resulting in a similar pattern of copy numbers and SNP distribution in both groups. Within further project ᴀow we aim to enlarge the number of affected patients to increase validity of our results.
CNV in human cystathionine-beta-synthase gene:
N=405 patients with severe sepsis/septic shock and n=405 age and gender matched controls were genotyped for the VNTR and hitherto non reported haplotypes of CBS. We found significant deviation of the VNTR length distribution towards longer CBS alleles in affected patients compared to non-septic controls. In both groups a similar pattern of haplotype distribution could be found, but septic patients showed a haplotype dependent difference in 28-survival.
Contact
Tel.: +49 (0)3641 - 9 32 22 25
Center for Sepsis Control and Care
Universitätsklinikum Jena
Erlanger Allee 101
07747 Jena