|Year : 2016 | Volume
| Issue : 3 | Page : 299-302
Human leucocyte antigen Class I and II alleles associated with anti-hepatitis C virus-positive patients of North India
M Chowdhry, RN Makroo, M Singh, S Agrawal, M Kumar, Y Thakur
Department of Transplant Immunology, Molecular Biology and Transfusion Medicine, Apollo Hospitals, New Delhi, India
|Date of Submission||19-Dec-2015|
|Date of Acceptance||30-Jun-2016|
|Date of Web Publication||12-Aug-2016|
Department of Transplant Immunology, Molecular Biology and Transfusion Medicine, Apollo Hospitals, New Delhi
Source of Support: None, Conflict of Interest: None
Purpose: Humans are the only known natural hosts of hepatitis C virus (HCV). This study was undertaken to examine the frequencies of human leucocyte antigens (HLAs) Class I and Class II genotype profiles in anti-HCV-infected patients of Northern India. Materials and Methods: From a period of January 2013 to August 2014, 148 anti-HCV-positive patients of North India referred to the Department of Molecular Biology and Transplant Immunology, Indraprastha Apollo Hospitals, New Delhi, for performing HLA typing were included in the study. Results: A*02, A*31 allele frequency decreased significantly in anti-HCV-positive patients. Frequencies for HLA-B loci did not reach any statistical significance. Among the Class II alleles, HLA-DRB1*03 and HLA-DRB1*10 were significantly higher in the patient population, and HLA-DRB1*15 was significantly decreased in the patient population as compared to the controls. Conclusion: HLA-A*33 was significantly increased as compared to control population and showed geographic variation in HCV-infected individuals of India.
Keywords: Hepatitis C virus, human leucocyte antigens, HLA-AFNx0133
|How to cite this article:|
Chowdhry M, Makroo R N, Singh M, Agrawal S, Kumar M, Thakur Y. Human leucocyte antigen Class I and II alleles associated with anti-hepatitis C virus-positive patients of North India. Indian J Med Microbiol 2016;34:299-302
|How to cite this URL:|
Chowdhry M, Makroo R N, Singh M, Agrawal S, Kumar M, Thakur Y. Human leucocyte antigen Class I and II alleles associated with anti-hepatitis C virus-positive patients of North India. Indian J Med Microbiol [serial online] 2016 [cited 2019 Oct 20];34:299-302. Available from: http://www.ijmm.org/text.asp?2016/34/3/299/188317
| ~ Introduction|| |
Hepatitis C virus (HCV) is a positive stranded RNA and enveloped virus. It belongs to the genus Hepacivirus of the family Flaviviridae. Fifteen percent of the individuals acquiring HCV infection clear it, whereas in remaining 85%, it may progress to chronic liver disease. The progression to chronicity depends on variable viral and host factors. The viral load and genotype have been prognostically implicated.
Human leucocyte antigens (HLAs) are encoded by major histocompatibility complex (MHC) located on short arm of chromosome no 6. HLA molecules bind and present peptide to T lymphocytes in cell-mediated immune response and play a key role in shaping the T-cell repertoire on it and are also associated with allograft rejections. HLA antigens are inherited in a codominant manner from parents by the offsprings. HLA has become an important tool for understanding the pathogenesis of various infectious diseases. HLA allele or haplotype inherited by an individual can predict several risk and protective factors related to infections caused by various agents.
HLA is one of the host factors, being reported to be associated with HCV infection. Various HLA alleles have been linked with either persistence or clearance of the virus. Correlation of HLA type, sex and HCV viral genotype to treatment responses is reported. Furthermore, there are reports which correlate HLA type, HCV genotype and patient ethnicity. Several studies have identified the involvement of HLA with different outcomes of HCV infection but with variable results. Many studies have also revealed that the prevalence of HCV infection is significantly low in Indian population. 
| ~ Materials and Methods|| |
From a period of January 2013 to August 2014, 148 anti-HCV-positive patients of North India referred to the Department of Molecular Biology and Transplant Immunology, Indraprastha Apollo Hospitals, New Delhi, for performing HLA typing (HLA A-B-DRB1) were included in the study. Out of these, six patients were positive for both anti-HCV antibodies and hepatitis B surface antigen (HBsAg). Healthy and unrelated, 154 individuals from the same ethnic background, who were negative for anti-HCV, anti-HIV antibodies and HBsAg were taken as controls.
Human leucocyte antigens typing
Low-resolution HLA typing for HLA-A, B, DR loci was performed by polymerase chain reaction sequence-specific primer (SSP) method (HLA-ABDR Invitrogen) using genomic DNA extracted from peripheral blood mononuclear cells by pure link genomic DNA extraction kit (Invitrogen). The primer set (AllSet+™ Gold SSP) contained 5' and 3' primers for grouping the HLA-A*01:01 to *80:01 alleles, 5' and 3' primers for grouping the B*07:02 to*83:01 alleles, 5' and 3' primers for grouping the DRB1*01:01 to DRB1*16:16. Amplified products were run on 2% agarose gel and gel image captured in Gel Documentation system and interpreted by Unimatch 6.0 CE-IVD software (Life Technologies Corporation).
The allele frequencies, odds ratio, Chi-square test and P values were calculated. P < 0.05 is considered to be statistically significant.
| ~ Results|| |
When compared to the control population, it was observed that among the Class I alleles-(HLA-A, HLA-B), A*33 allele (odd ratio 1.85, P [Fisher exact] = 0.046) was increased significantly as compared to the control population. Similarly, A*02, A*31 allele frequency was decreased significantly in anti-HCV-positive patients as compared to control population.
In HLA-B locus, B*27 allele frequency was decreased significantly in anti-HCV-positive patients as compared to control population. However, the frequencies for HLA-B loci did not reach any statistical significance when compared with the control population.
Among the Class II alleles, HLA-DRB1*03 (odd ratio 1.89, P [Fisher's exact] = 0.005) and HLA-DRB1*10 (odd ratio 2.81, P [Fisher's exact] = 0.009) were statistically significantly higher in the patient population, and HLA-DRB1*15 was significantly decreased in the patient population as compared to the controls.
HLA distribution in anti-HCV-positive individuals and controls is tabulated in [Table 1].
|Table 1: Frequency of human leucocyte antigens loci in anti - hepatitis C virus - positive patients |
Click here to view
| ~ Discussion|| |
Genes located within the MHC play a major role in influencing the immune response against infectious agents. Optimal interactions between T-cell receptor, MHC Class I or II molecules and antigenic viral peptides are required for an adequate immune response. Thus, the expression of particular HLA specificities might lead to a defective antigen presentation, allowing the HCV infection.
Different allele and haplotype associations have been repeatedly reported with HCV, which varies with ethnicity and geographical location of the patients. We undertook this study to examine the frequencies of HLA Class I and Class II genotype profiles in anti-HCV infected patients of Northern India.
In the present study, HLA-A*33 was significantly increased as compared to control population. However, a study conducted from Western India indicates that the same allele was significantly decreased.  This was interesting as this allele showed a geographic variation with respect to HCV-positive patients.
HLA-DRB1*03 was found to be associated with HCV infection in our study group. Several other supportive findings have been demonstrated time and again in various study models. ,, Tripathy et al.  found that a significant increase in the allele DRB1*03 was present in the HCV-positive patients of Western India. Other alleles significantly increased in the HCV-infected patients as compared to control population in their study were HLA-A*03, A*26, A*32, A*66, B*08, B*15, B*55 and B*57, DRB1*12, DRB1*16 and DQB1*03. Furthermore, they found that the HLA Class II locus haplotype DRB1*11-DQB1*03 was significantly increased among HCV-infected individuals.
Interestingly, this HLA-DRB1*03, to be more specific, HLA-DRB1*03:01 is commonly associated with many autoimmune diseases such as rheumatoid arthritis  and has a positive association with systemic lupus erythematosus and autoimmune hepatitis. , In our study, HLA typing was performed only at a low resolution; therefore, it was not possible to determine the prevalence at the allelic level. However, it still gives us an insights into the role of this HLA gene and its association with various autoimmune diseases.
Asti et al.  in their study found that the HLA-DRB1*10:01 was associated with the severity of the disease in HCV-infected individuals. This corroborated with our study wherein we observed a significant increase of HLA-DRB1*10 in HCV-infected individuals.
Wang et al.  showed that the HLA-A*02 shows opposing trends in different ethnic groups: Risk for Caucasians and protective for non-Caucasians. Although these associations were not statistically significant, interaction with race was evident. In our study as well, HLA-A*02 was significantly decreased as compared to the patient population as most of the patients included in our study were non-Caucasians.
No supportive evidence for association of HCV with A*31 was found. This needs to be studied further with larger study population from different ethnicities to prove it conclusively.
| ~ Conclusion|| |
The findings of the present study were a significant increase among the allele frequencies of HLA-A*33, DRB1*03 and DRB1*10, and a significant decrease in frequency of A*02, A*31, DRB1*15 alleles among patients compared to controls.
HLA-A*33 was significantly increased as compared to control population and showed geographic variation in HCV-infected individuals of India.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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