Association between HLA variations and chronic hepatitis B virus infection in Saudi Arabian patients.
Hepatitis B virus (HBV) infection is a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. Human leukocyte antigens (HLAs) play an important role in the regulation of immune response against infectious organisms, including HBV. Recently, several genome-wide association (GWAS) studies have shown that genetic variations in HLA genes influence disease progression in HBV infection. The aim of this study was to investigate the role of HLA genetic polymorphisms and their possible role in HBV infection in Saudi Arabian patients. Variations in HLA genes were screened in 1672 subjects who were divided according to their clinical status into six categories as follows; clearance group, inactive carriers, active carriers, cirrhosis, hepatocellular carcinoma (HCC) patients and uninfected healthy controls. Three single nucleotide polymorphisms (SNPs) belonged to HLA-DQ region (rs2856718, rs7453920 and rs9275572) and two SNPs belonged to HLA-DP (rs3077 and rs9277535) were studied. The SNPs were genotyped by PCR-based DNA sequencing (rs2856718) and allele specific TaqMan genotyping assays (rs3077, rs7453920, rs9277535 and rs9275572). The results showed that rs2856718, rs3077, rs9277535 and rs9275572 were associated with HBV infection (p = 0.0003, OR = 1.351, CI = 1.147-1.591; p = 0.041, OR = 1.20, CI = 1.007-1.43; p = 0.045, OR = 1.198, CI = 1.004-1.43 and p = 0.0018, OR = 0.776, CI = 0.662-0.910, respectively). However, allele frequency of rs2856718, rs7453920 and rs9275572 were found more in chronically infected patients when compared to clearance group infection (p = 0.0001, OR = 1.462, CI = 1.204-1.776; p = 0.0178, OR = 1.267, CI = 1.042-1.540 and p = 0.010, OR = 0.776, CI = 0.639-0.942, respectively). No association was found when polymorphisms in HLA genes were compared in active carriers versus cirrhosis/HCC patients. In conclusion, these results suggest that variations in HLA genes could affect susceptibility to and clearance of HBV infection in Saudi Arabian patients.
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia ; Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia.
Ahmed A
AA
Al-Qahtani
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Mashael R
MR
Al-Anazi
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia ; Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia.
Ayman A
AA
Abdo
Hepatobiliary Sciences and Liver Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia ; Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia.
Faisal M
FM
Sanai
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia ; Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia.
Waleed
W
Al-Hamoudi
Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia ; Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia.
Khalid A
KA
Alswat
Department of Medicine, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Hamad I
HI
Al-Ashgar
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Nisreen Z
NZ
Khalaf
Department of Biostatistics, Epidemiology & Scientific Computing, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Abdelmoneim M
AM
Eldali
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Nisha A
NA
Viswan
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Mohammed N
MN
Al-Ahdal
D000328:Adult; D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006682:HLA-DP Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000235:genetics; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia / Q000453:epidemiology; D055815:Young Adult
D006680:HLA Antigens; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens