The association between the genetic polymorphism of HLA-DQA1, DQB1, and DRB1 and serum alanine aminotransferase levels in chronic hepatitis C in the Chinese population.
OBJECTIVE
To investigate a possible association between HLA genes with serum alanine aminotransferase (ALT) levels and evaluate whether the HLA-DQA1, DQB1, and DRB1 genes could influence the development of liver damage in chronic hepatitis C.


METHODS
A total of 145 patients with chronic hepatitis C virus (HCV) infection (36 patients with persistently normal ALT values; 109 patients with elevated ALT levels) and 160 uninfected healthy controls were examined for HLA-DQA1, DQB1, and DRB1 molecules by using polymerase chain reaction-sequencing based typing (PCR-SBT).


RESULTS
Among the patients chronically infected with HCV, the frequencies of DQA1*0501, DQB1*0301, and DRB1*0401 alleles were significantly increased in the normal ALT group compared with those with abnormal ALT levels, whereas that of DQB1*0201 was significantly lower. As compared to uninfected healthy controls, DQA1*0501, DQB1*0301, and DRB1*0401 allele frequencies were also statistically higher in the normal ALT group, whereas that of DQB1*0201 was the inverse. The haplotype frequencies of DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 were found to be significantly higher in the normal ALT group. Multivariate logistic regression indicated that female sex, and the DQB1*0301 allele and DRB1*0401 allele were independently associated with normal ALT values, whereas DQB1*0201 allele was the inverse.


CONCLUSIONS
These results suggest that particular HLA alleles may have an influence on the serum ALT level of chronic HCV infection as a host genetic factor in the Chinese population. The DQA1*0501, DQB1*0301, and DRB1*0401 alleles, and the DQA1*0301-DQB1*0301, DQA1*0501-DQB1*0301, and DRB1*1101-DQB1*0301 haplotypes seem to be associated with low hepatitis activity; whereas DQB1*0201 allele is closely correlated with the progression of liver injury in chronic HCV infection.
Yu
Rong-Bin
RB
Department of Epidemiology and Biostatistics, School of Public Health, Jiangsu Province Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, China.
Hong
Xin
X
Ding
Wei-Liang
WL
Tan
Yong-Fei
YF
Zhang
Yong-Xiang
YX
Sun
Nan-Xiong
NX
Wu
Guan-Ling
GL
Zhan
Sheng-Wei
SW
Ge
Da-Fang
DF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004796:Clinical Enzyme Tests; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D008562:Membrane Glycoproteins; D000410:Alanine Transaminase