A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection.
OBJECTIVE
HCV-infection leads to development of liver fibrosis, causing morbidity and mortality. Multiple factors influence the progression of fibrosis, including genetic factors. Since HCV is an RNA virus, a role for TLR7 in the immune response against HCV is likely. No systematic analysis of TLR7 single nucleotide polymorphisms (SNPs) has been published.


METHODS
We sequenced TLR7 in 52 women and investigated SNPs with an allele frequency >5% in 807 patients with chronic HCV-infection by melting curve analysis. We analyzed the effect of TLR7 SNPs on grade of inflammation and stage of fibrosis as determined by liver biopsy.


RESULTS
We detected five TLR7 SNPs, three of which showed a frequency >5%. One variant, c.1-120T>G, was more common in patients with no or little inflammation than in patients with grades 2-4 (10.7% vs. 6.1%; P=0.034). The variant was also enriched in patients with no or little fibrosis compared to those with higher stages (12.6% vs. 6.6%; P=0.005). The difference was fully attributable to male patients.


CONCLUSIONS
This is the first analysis of TLR7 SNPs in patients with chronic HCV-infection. Our data suggest that the c.1-120G TLR7 allele offers protection from the development of inflammation and fibrosis in male patients with chronic HCV-infection.
Schott
Eckart
E
Department of Hepatology and Gastroenterology, CVK, Charité Universitätsmedizin Berlin, Germany.
Witt
Heiko
H
Neumann
Konrad
K
Taube
Stefan
S
Oh
Djin-Ye
DY
Schreier
Eckart
E
Vierich
Sandra
S
Puhl
Gero
G
Bergk
Alexandra
A
Halangk
Juliane
J
Weich
Viola
V
Wiedenmann
Bertram
B
Berg
Thomas
T
D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006147:Guanine; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D012737:Sex Factors; D013941:Thymine; D051199:Toll-Like Receptor 7 / Q000235:genetics*
C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D006147:Guanine; D013941:Thymine