HLA class II allele polymorphism in an outbreak of chikungunya fever in M iddle A ndaman, I ndia

Summary A sudden upsurge of fever cases with joint pain was observed in the outpatient department, C ommunity H ealth C entre, R angat during J uly– A ugust 2010 in R angat M iddle A ndaman, I ndia. The aetiological agent responsible for the outbreak was identified as chikungunya virus ( CHIKV ), by using RT‐PCR and IgM ELISA . The study investigated the association of polymorphisms in the human leucocyte antigen class II genes with susceptibility or protection against CHIKV . One hundred and one patients with clinical features suggestive of CHIKV infection and 104 healthy subjects were included in the study. DNA was extracted and typed for HLA ‐ DRB 1 and DQB 1 alleles. Based on the amino acid sequences of HLA ‐ DQB 1 retrieved from the IMGT / HLA database, critical amino acid differences in the specific peptide‐binding pockets of HLA ‐ DQB 1 molecules were investigated. The frequencies of HLA ‐ DRB 1 alleles were not significantly different, whereas lower frequency of HLA ‐ DQB 1*03:03 was observed in CHIKV patients compared with the control population [ P  = 0·001, corrected P  = 0·024; odds ratio ( OR )  = 0, 95% confidence interval (95% CI ) 0·0–0·331; Peto's OR = 0·1317, 95% CI 0·0428–0·405). Significantly lower frequency of glutamic acid at position 86 of peptide‐binding pocket 1 coding HLA ‐ DQB 1 genotypes was observed in CHIKV patients compared with healthy controls ( P  = 0·004, OR  = 0·307, 95% CI 0·125–0·707). Computational binding predictions of CD 4 epitopes of CHIKV by N et MHCII revealed that HLA ‐ DQ molecules are known to bind more CHIKV peptides than HLA ‐ DRB 1 molecules. The results suggest that HLA ‐ DQB 1 alleles and critical amino acid differences in the peptide‐binding pockets of HLA ‐ DQB 1 alleles might have role in influencing infection and pathogenesis of CHIKV .