Indian Journal of Medical Microbiology IAMM  | About us |  Subscription |  e-Alerts  | Feedback |  Login   
  Print this page Email this page   Small font sizeDefault font sizeIncrease font size
 Home | Ahead of Print | Current Issue | Archives | Search | Instructions  
Users Online: 2989 Official Publication of Indian Association of Medical Microbiologists 
  Search
 
  
 ~  Similar in PUBMED
 ~  Search Pubmed for
 ~  Search in Google Scholar for
 ~Related articles
 ~  Article in PDF (409 KB)
 ~  Citation Manager
 ~  Access Statistics
 ~  Reader Comments
 ~  Email Alert *
 ~  Add to My List *
* Registration required (free)  

 
 ~  Abstract
 ~ Introduction
 ~  Materials and Me...
 ~ Results
 ~ Discussion
 ~ Conclusion
 ~  References
 ~  Article Tables

 Article Access Statistics
    Viewed1688    
    Printed26    
    Emailed0    
    PDF Downloaded126    
    Comments [Add]    

Recommend this journal

 


 
  Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 34  |  Issue : 3  |  Page : 299-302
 

Human leucocyte antigen Class I and II alleles associated with anti-hepatitis C virus-positive patients of North India


Department of Transplant Immunology, Molecular Biology and Transfusion Medicine, Apollo Hospitals, New Delhi, India

Date of Submission19-Dec-2015
Date of Acceptance30-Jun-2016
Date of Web Publication12-Aug-2016

Correspondence Address:
M Chowdhry
Department of Transplant Immunology, Molecular Biology and Transfusion Medicine, Apollo Hospitals, New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.188317

Rights and Permissions

 ~ Abstract 

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 Top


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. [1]


 ~ Materials and Methods Top


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).

Statistical analysis

The allele frequencies, odds ratio, Chi-square test and P values were calculated. P < 0.05 is considered to be statistically significant.


 ~ Results Top


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 Top


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. [1] 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. [2],[3],[4] Tripathy et al. [1] 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 [5] and has a positive association with systemic lupus erythematosus and autoimmune hepatitis. [6],[7] 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. [8] 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. [9] 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 Top


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

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Tripathy AS, Shankarkumar U, Chadha MS, Ghosh K, Arankalle VA. Association of HLA alleles with hepatitis C infection in Maharashtra, Western India. Indian J Med Res 2009;130:550-5.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
Thio CL, Carrington M, Marti D, O'Brien SJ, Vlahov D, Nelson KE, et al. Class II HLA alleles and hepatitis B virus persistence in African Americans. J Infect Dis 1999;179:1004-6.  Back to cited text no. 2
    
3.
McKiernan SM, Hagan R, Curry M, McDonald GS, Kelly A, Nolan N, et al. Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source. Hepatology 2004;40:108-14.  Back to cited text no. 3
    
4.
Kuniholm MH, Kovacs A, Gao X, Xue X, Marti D, Thio CL, et al. Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia. Hepatology 2010;51:1514-22.  Back to cited text no. 4
    
5.
Jun KR, Choi SE, Cha CH, Oh HB, Heo YS, Ahn HY, et al. Meta-analysis of the association between HLA-DRB1 allele and rheumatoid arthritis susceptibility in Asian populations. J Korean Med Sci 2007;22:973-80.  Back to cited text no. 5
    
6.
Czaja AJ. Genetic factors affecting the occurrence, clinical phenotype, and outcome of autoimmune hepatitis. Clin Gastroenterol Hepatol 2008;6:379-88.  Back to cited text no. 6
    
7.
Fernando MM, Stevens CR, Sabeti PC, Walsh EC, McWhinnie AJ, Shah A, et al. Identification of two independent risk factors for lupus within the MHC in United Kingdom families. PLoS Genet 2007;3:e192.  Back to cited text no. 7
    
8.
Asti M, Martinetti M, Zavaglia C, Cuccia MC, Gusberti L, Tinelli C, et al. Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease. Hepatology 1999;29:1272-9.  Back to cited text no. 8
    
9.
Wang JH, Zheng X, Ke X, Dorak MT, Shen J, Boodram B, et al. Ethnic and geographical differences in HLA associations with the outcome of hepatitis C virus infection. Virol J 2009;6:46.  Back to cited text no. 9
    



 
 
    Tables

  [Table 1]



 

Top
Print this article  Email this article
 

    

2004 - Indian Journal of Medical Microbiology
Published by Wolters Kluwer - Medknow

Online since April 2001, new site since 1st August '04