Genetic susceptibility of eight nonsynonymous polymorphisms in HLA-DRB1 gene to hepatocellular carcinoma in Han Chinese.
Backgrounds and Objective: Mounting evidence suggests that human leukocyte antigen (HLA) plays a central role in anti-virus and tumor defense. To test whether genetic variation in HLA-DRB1 gene, a key component of HLA system, can predict its predisposition to hepatocellular carcinoma (HCC), we thereby conducted an association study by genotyping 8 nonsynonymous polymorphisms in HLA-DRB1 gene among 257 HCC patients and 264 controls.


RESULTS
All polymorphisms respected the Hardy-Weinberg equilibrium. The genotypes and alleles of rs17879599 differed significantly between patients and controls after Bonferroni correction (both P < 0.001), and the power to detect this significance was 94.4%. After adjusting for age, gender, smoking, drinking and hepatitis infection, the mutant allele of rs17879702 was significantly associated with an increased risk for HCC under additive (odds ratio [OR] = 2.12, 95% confidence interval [CI]: 1.20-4.02, P = 0.004) and dominant (OR = 2.51, 95% CI: 1.39-2.96, P = 0.004) models. Haplotype analysis indicated that haplotype A-T-C-T-G-C-T-A (alleles ordered by rs199514452, rs201540428, rs201614260, rs17879702, rs17880292, rs17879599, rs17424145 and rs35445101) was overrepresented in patients and enhanced predisposition to HCC (adjusted OR = 2.72, 95% CI: 1.24-5.78, P = 0.004). In cumulative analysis, carriers of 7-9 unfavorable alleles had a 2.41-fold (95% CI: 1.18-4.92, P = 0.016) increased risk for HCC after adjusting for confounding factors relative to those possessing 4 or less unfavorable alleles.


METHODS
Genotypes were determined by ligase detection reaction. HCC patients were newly diagnosed, histopathologically confirmed or previously untreated and controls were cancer-free.


CONCLUSIONS
Our findings suggest an independent leading contribution of rs17879599 in the 2nd exon of HLA-DRB1 gene to HCC risk in Han Chinese.
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Yanhui
Y
Shi
Department of Pharmacy, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Weiyu
W
Zhai
Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Bin
B
Wang
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Dongmei
D
Zhao
Department of Cardiology, Hospital of Traditional Chinese Medicine of Qiqihar, Qiqihar, Heilongjiang, China.
He
H
Jin
Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Yuefei
Y
Wang
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Jidong
J
Zhang
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Hongjun
H
An
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Zhongze
Z
Fu
Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Kun
K
Zhao
Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Changzhu
C
Lu
D000368:Aged; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D014408:Biomarkers, Tumor; D059811:HLA-DRB1 Chains
Han Chinese; genetic predisposition; hepatocellular carcinoma; human leukocyte antigen; non-synonymous polymorphism