Influence of interleukin-10 gene promoter polymorphisms on disease progression in patients chronically infected with hepatitis B virus.
OBJECTIVE
The role of host genetic factors in chronic hepatitis B virus (HBV) infection is not fully understood. We studied the influence of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) gene promoter polymorphisms on disease progression in HBV carriers.


METHODS
The sample population included 213 Japanese HBV carriers and 52 healthy volunteers. Of 213 HBV carriers, 66 were considered to be asymptomatic carriers based on the sustained normalization of serum ALT together with seropositivity for the antibody to hepatitis B e antigen (anti-HBe), and 147 were found to have chronic progressive liver disease including cirrhosis. Five biallelic polymorphisms in the TNF-alpha gene promoter and three biallelic polymorphisms in the IL-10 gene promoter were analyzed by polymerase chain reaction in combination with direct sequencing or restriction fragment length polymorphism assay.


RESULTS
Allelic distributions of both gene promoters were not significantly different between HBV carriers and healthy volunteers. In HBV carriers, the TNF-alpha gene promoter polymorphisms were not linked to disease progression. In contrast, allelic frequencies of T and A at positions -819 and -592, respectively, in the IL-10 gene promoter, as well as the frequencies of ATA haplotype at positions -1082/-819/-592 (which is characterized with low capacity for IL-10 production), were significantly higher in asymptomatic carriers than in patients with chronic progressive liver disease. Even after adjusting for individuals positive for anti-HBe, such a relationship could be found between the two groups.


CONCLUSIONS
In chronic HBV infection, inheritance of the IL-10 gene promoter polymorphisms is involved in a host genetic factor that is relevant to disease progression.
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Seiji
S
Miyazoe
Keisuke
K
Hamasaki
Keisuke
K
Nakata
Yuji
Y
Kajiya
Kayo
K
Kitajima
Kazuhiko
K
Nakao
Manabu
M
Daikoku
Hiroshi
H
Yatsuhashi
Michiaki
M
Koga
Michitami
M
Yano
Katsumi
K
Eguchi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018450:Disease Progression; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10