Evaluation of complement factor 5 variants as genetic risk factors for the development of advanced fibrosis in chronic hepatitis C infection.
OBJECTIVE
Intercross studies in inbred mice susceptible or resistant to liver fibrosis revealed complement factor 5 as a quantitative trait gene associated with the development of fibrosis. In 277 patients with hepatitis C, two C5 SNPs, rs17611 and rs2300929, have been associated with advanced fibrosis.


METHODS
We investigated the association of these C5 SNPs with advanced fibrosis in 1435 HCV infected patients and in 1003 patients with other liver diseases. We performed genotyping with melting curve analysis using fluorescence resonance energy transfer probes in the LightCycler.


RESULTS
The defined high-risk genotypes (AA and TT) and alleles (A and T) were not associated with advanced fibrosis in HCV patients when Chi square testing and logistic regression analysis were applied (rs17611A 0.45 in F0-1 vs. 0.43 in F2-4, P=0.31; rs2300929T 0.91 F0-1 and 0.91 in F2-4, P=0.82). In the group of patients with liver diseases other than HCV we neither found an association of the C5 SNPs with advanced fibrosis nor an overrepresentation of the SNPs in patients with cirrhosis.


CONCLUSIONS
We found no evidence that these C5 SNPs are genetic risk factors for the development of advanced fibrosis in chronic HCV infection or other chronic liver diseases.
Halangk
Juliane
J
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany.
Sarrazin
Christoph
C
Neumann
Konrad
K
Puhl
Gero
G
Mueller
Tobias
T
Teuber
Gerlinde
G
Klinker
Hartwig
H
Hinrichsen
Holger
H
Buggisch
Peter
P
Landt
Olfert
O
Weich
Viola
V
Bergk
Alexandra
A
Wiedenmann
Bertram
B
Neuhaus
Peter
P
Berg
Thomas
T
Witt
Heiko
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003182:Complement C5 / Q000235:genetics*; D005060:Europe; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D003182:Complement C5