Genetische Haplotypanalyse des distalen CXC-Chemokinclusters bei Patienten mit symptomatischer Cholelithiasis

Symptomatic gallstones are a compex disorder characterized by multiple interactions of various environmental and genetic risk factors. The present study was supposed to clarify if patients with symptomatic gallstones show a higher predisposition to inflammation and if this is due to variations of genes that encode inflammation proteins. According to a murine quantitative trait locus (QTL) analysis, in which the distal CXC chemokine cluster on murine chromosome 5 was identified as a potential modifier of liver fibrosis, we searched for appropriate polymorphisms of the genes CXL9, 10 and 11 on the human chromosome 4. To identify an association between genetic variations and symptomatic gallstones 8 SNPs that cover the distal CXC chemokine cluster were genotyped in three samples of patients with symptomatic and asymptomatic gallstones and stone-free patients (106 persons, respectively). There was a significant association between the allel frequencies of patients with symptomatic gallstones and stone-free patients for the SNP rs3733236 on the gene CXL9 (p=0,046). In a subsequent haplotype analysis we identified the fourth most frequent haplotype (dCXC_4) that is tagged by the SNP rs3733236 as a functional haplotype. In patients with symptomatic gallstones dCXC_4 was significant less frequent than in stone-free patients (p<0,03). The functionality of this haplotype was pointed up in a test series of healthy individuals in which CXCL9 serum concentrations were significantly associated with the presence of this CXC haplotype (p<0,001). Furthermore there was a significant negative correlation with the serum concentration of glucose at the presence of dCXC_4 (p=0,036). At last we examined exogenous risk factors to show an influence on the pathogenesis of symptomatic gallstones. We found a significant association between symptomatic gallstones and the body-mass-index (BMI) (p=0,04) and an inverse association to the serum cholesterol level (p=0,005). The present study underlies the importance of genetic risk factors involved in the development of symptomatic gallstones and contributes to the clarification of the molecular pathomechanism of this common disease. Prospective studies should focus on the identification of further candidate genes that contribute to this complex disorder. Together with exogenous risk factors the knowledge of genetic predispositions could help to ascertain individual risk assessment, prevention and therapy of symptomatic gallstones.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2009

Author dc:creator

• Derichs, Cornelia

Contributors dc:contributor

• Wasmuth, Hermann E.

• info:eu-repo/classification/ddc/610
• Gallensteinleiden
• Chemokine
• Haplotyp
• Medizin
• Polymorphismen
• Haplotypanalyse
• symptomatic gallstones
• polymorphisms
• haplotype analysis

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113456%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51141