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Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India

  • Rathika, Chinniah (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University) ;
  • Murali, Vijayan (Department of Biotechnology and Genetic Engineering, Bharathidasan University) ;
  • Dhivakar, Mani (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University) ;
  • Kamaraj, Raju (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University) ;
  • Malini, Ravi Padma (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University) ;
  • Ramgopal, Sivanadham (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University) ;
  • Balakrishnan, Karuppiah (Department of Immunology, School of Biological Sciences, Madurai Kamaraj University)
  • Published : 2016.05.01

Abstract

Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; p< $3.5{\times}10^{-4}$), DRB1*14-DQB1*0501 (OR=6.51; p<0.039) and A*11-B*07 (OR=3.95; p<0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; p<0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions ${\beta}9$ and ${\beta}37$ and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.

Keywords

Human leukocyte antigen;alleles/haplotypes;cervical cancer;susceptibility;protection;South India

Acknowledgement

Supported by : Madurai Kamaraj University

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