Lower copy numbers of the chemokine CCL3L1 gene in patients with chronic hepatitis C.
OBJECTIVE
Recently, variation of gene copy numbers was recognized as a novel type of common genetic diversity, but its impact on viral hepatitis is unknown. Here, we determine the influence of copy number variation on the susceptibility and disease severity in hepatitis C virus (HCV) infection, investigating copy number variants (CNVs) of the chemokine CCL3L1 gene, which encodes a potent CCR5 ligand.


METHODS
CNVs were determined in 254 patients with chronic hepatitis C, 144 HCV/HIV co-infected patients, and 210 HCV negative controls, using quality-controlled real-time fluorescent dye-labeled quantitative PCR. Liver biopsies were obtained from HCV infected patients.


RESULTS
Copy numbers of the CCL3L1 gene range from 0 to 12 (mean 2.7+/-1.4 copies). Patients with two or less copies are over-represented in the HCV infected cohort compared to HCV negative controls (odds ratio [OR] 1.54; p=0.02). CCL3L1 copies are shifted to lower numbers in HCV infected patients (means 2.6 vs. 2.9 in controls; p=0.011). HCV/HIV co-infected patients carry even lower CCL3L1 copy numbers compared to controls (means 2.2 vs. 2.9; p<0.001), with a higher proportion of patients possessing two or less copies (OR=3.42; p<0.001). No association was detected between CCL3L1 copy numbers and histological grades of inflammation or stages of fibrosis.


CONCLUSIONS
Lower CCL3L1 gene copy number compared to the population median is associated with chronic hepatitis C. Copy number variation of host genes represents a novel class of genetic diversity associated with viral hepatitis.
Grünhage
Frank
F
Department of Medicine II, Saarland University Hospital, Saarland University, Homburg, Germany. frank.gruenhage@uks.eu
Nattermann
Jacob
J
Gressner
Olav A
OA
Wasmuth
Hermann E
HE
Hellerbrand
Claus
C
Sauerbruch
Tilman
T
Spengler
Ulrich
U
Lammert
Frank
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D055815:Young Adult
C492767:CCL3L1 protein, human; D019742:Chemokines, CC; D019713:Receptors, CCR5