Gender susceptibility to chronic hepatitis C virus infection associated with interleukin 10 promoter polymorphism.
Elevated levels of interleukin 10 (IL-10) were previously described for chronically hepatitis C virus (HCV)-infected patients. We determined by a sequence-specific oligonucleotide probing technique the IL-10 promoter genotypes in 286 Argentinean HCV patients grouped according to disease outcome. The GG genotype (position -1082) is known to be associated with high IL-10 production, GA is considered an intermediate producer, and AA is associated with low IL-10 production. We found an increase in frequency of the GG genotype in female patients who do not eliminate the virus (RNA(+)). In these patients, the GG frequency was 0.19, versus 0.10 in controls (P = 0.03). This association became more significant in those RNA(+) female patients with elevated hepatic transaminases (GG frequency of 0.25; P = 0.0013). Additionally, this genotype frequency was higher in noncirrhotic female patients than in controls (GG frequency for noncirrhotic female patients was 0.31; P = 0.009). In RNA(-) patients, the GA frequency was elevated compared with that in controls (GA frequency of 0.76 in RNA(-) patients versus 0.48 in controls; P = 0.01), that in all HCV patients (GA frequency of 0.43; P = 0.001), and that in RNA(+) patients (GA frequency of 0.40; P = 0.0005). We conclude that a gender effect is observed with women carrying the GG high IL-10 producer genotype. The higher levels of IL-10 present in those individuals are associated with a higher risk of an inefficient clearance of the HCV and the development of a chronic HCV infection together with a lower risk of progression to cirrhosis in female patients.
Paladino
Natalia
N
División Inmunogenética, Hospital de Clínicas José de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Av. Córdoba 2351, Buenos Aires 1120, Argentina.
Fainboim
Hugo
H
Theiler
Graciela
G
Schroder
Teresa
T
Muñoz
Alberto Eduardo
AE
Flores
Ana Claudia
AC
Galdame
Omar
O
Fainboim
Leonardo
L
D000328:Adult; D000368:Aged; D005260:Female; D005355:Fibrosis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006526:Hepatitis C / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012737:Sex Factors
D016753:Interleukin-10