Association of polymorphisms of interleukin-18 gene promoter region with chronic hepatitis B in Chinese Han population.
OBJECTIVE
To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population.


METHODS
Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls.


RESULTS
Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of -137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (chi2 = 8.55, P = 0.003<0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (chi2 = 6.03, P = 0.014<0.05).


CONCLUSIONS
The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.
Zhang
Ping-An
PA
Department of Laboratory Science, Affiliated Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
Wu
Jian-Min
JM
Li
Yan
Y
Yang
Xiang-Sheng
XS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics / Q000254:growth & development*; D019694:Hepatitis B, Chronic / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D014779:Virus Replication
D004279:DNA, Viral; D020382:Interleukin-18