ABSTRACT
OBJECTIVE: To assess the association of haplotype of HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection in Han population of north China. METHODS: Two hundred and seven chronic hepatitis B (HB) patients, two hundred and twelve chronic asymptomatic hepatitis B virus (HBV) carriers (HBV carrier) and one hundred and forty-eight self-limited HBV infection were investigated for HLA-DRB1 and HLA-DQA1 alleles by sequence specific-polymerase chain reaction (PCR-SSP). RESULTS: The frequency of DRB1*04-DQA1*0301 haplotype was 10.03% in self-limited HBV infection subjects, significantly higher than that in chronic HB patients (3.66%) (P=0.0005)ûthe frequency of DRB1*15/*16-DQA1*0102 haplotype was 6.80% in self-limited HBV infection subjects, significantly higher than 1.94% in chronic HB patients (P=0.0012) and 1.65% in asymptomatic HBV carriers (P=0.0004)ûwhile the frequency of DRB1*04-DQA1*0302 haplotype was 3.10% in chronic HB patients, higher than that in self-limited HBV infection subjects (0.39%) (P=0.0077). CONCLUSION: Individuals with different haplotypes composed of HLA-DRB1 and HLA-DQA1 might have different outcomes of HBV infection.
Subject(s)
HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Hepatitis B/genetics , Adolescent , Adult , Alleles , Female , Gene Frequency , Genetic Predisposition to Disease/genetics , HLA-DQ alpha-Chains , HLA-DRB1 Chains , Haplotypes , Humans , Male , Middle Aged , Polymerase Chain ReactionABSTRACT
OBJECTIVE: To assess the association of polymorphisms of human leucocyte antigen (HLA) -DRB1 and -DQA1 region allele with outcomes of hepatitis B virus (HBV) infection in Han population of north China. METHODS: A total of 207 chronic hepatitis B (HB) patients, 212 chronic asymptomatic HBV carriers (HBV carrier), and 148 self-limited HBV infection were recruited to examine the association between gene polymorphisms and outcomes of HBV infection. Polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to genotype HLA-DRB1 and HLA-DQA1 loci. RESULTS: The frequency of HLA-DQA1 * 0301 in chronic HB patients (14.81%) was significantly lower than those in HBV carriers (25.24%) and self-limited HBV infection subjects (25.00%) (Pc = 0.002; Pc = 0.007). The frequency of HLA-DQA1 * 0102 in self-limited HBV infection subjects (8.78%) was significantly higher than those in chronic HB patients (2.18%) and HBV carriers (1.89%) (Pc = 0.000; P = 0.000). In addition, the frequency of HLA-DQA1 * 0302 in self-limited HBV infection subjects (4.05%) was significantly lower than that in chronic HB patients (11.41%) (Pc = 0.005). HLA-DQA1 * 0302 was demonstrated to be risk factors of chronic HBV (OR = 3.913, P = 0.0006), while HLA-DQA1* 0102 and HLA-DQA1 * 0301 to be protective factors against chronic HBV (OR = 0.200, P = 0.0004; OR = 0.258, P = 0.0000) after age, sex, smoking and drinking were adjusted by logistic regression analysis. There were positive interactions between drinking and HLA-DQA1 * 0102 [interaction index (II) = 1.49] or HLA-DQA1 * 0302 (II = 12.12). There were negative interactions between drinking and HLA-DQA1 * 0301 (II = 0.78) CONCLUSIONS: The subjects with HLA-DQA1 * 0302 allele have an increased risk to chronic HB infection compared with other subjects without this allele, while HLA-DQA1 * 0301 and HLA-DQA1 * 0102 are associated with HBV clearness. Gene-environment interaction can affect the outcomes of HBV infection.
Subject(s)
Asian People/genetics , Genetic Predisposition to Disease/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Hepatitis B/genetics , Polymorphism, Genetic , Adolescent , Adult , Alcohol Drinking , Case-Control Studies , Environment , Female , Gene Frequency , HLA-DQ alpha-Chains , HLA-DRB1 Chains , Hepatitis B/ethnology , Humans , Male , Middle Aged , Risk FactorsABSTRACT
AIM: To clarify whether -238G/A polymorphism of tumor necrosis factor-alpha (TNF-alpha) gene promoter region was associated with outcomes of hepatitis B virus (HBV) infection in Han population of northern China, and to analyze the gene-environment interaction between -238G/A polymorphism and cigarette smoking or alcohol consumption. METHODS: A case-control study was conducted to analyze the association of TNF-alpha gene promoter polymorphism with HBV infection outcomes. A total of 207 patients with chronic hepatitis B (HB) and 148 cases of self-limited HBV infection from Ditan Hospital and Shunyi District Hospital in Beijing, respectively were recruited. History of smoking and alcohol drinking was inquired by a questionnaire. The -238G/A polymorphism of TNF-alpha gene promoter was genotyped by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of GG and GA genotypes were 98.07% and 1.93% in chronic HB patients and 93.24% and 6.76% in self-limited HBV infection individuals, respectively (chi(2)=5.30, P=0.02). The frequency of G allele was significantly higher in patients with chronic HB that in individuals with self-limited HBV infection (99.03% vs 96.62%, chi(2)=5.20, P=0.02). Only modestly increased risk of onset of chronic HB was found in smokers (OR=1.40, 95% CI: 0.87-2.28, P=0.14) and drinkers (OR=1.26, 95%CI: 0.78-2.05, P=0.32). There was a positive interaction between genotype GG and cigarette smoking with an interaction index (II) of 2.95, or alcohol consumption with an II of 1.64. CONCLUSION: The -238G/A polymorphism of TNF-alpha gene promoter region is independently associated with different outcomes of HBV infection.
