HLA-DQB1 and -DPB1 allele profile in HIV infected patients with and without pulmonary tuberculosis of south India.
We made an attempt to find out whether Human Leucocyte Antigen (HLA)-DQB1 and -DPB1 alleles are associated with susceptibility or resistance to Human Immunodeficiency Virus (HIV) infection and development of pulmonary tuberculosis (PTB) in HIV infected patients. The allelic profile of HLA-DQB1 and -DPB1 was studied among HIV patients without pulmonary tuberculosis (HIV+PTB-) (n = 115), HIV patients with pulmonary TB (HIV+PTB+) (n = 59), HIV negative PTB patients (HIV-PTB+) (n = 110) and healthy controls (n=112) by polymerase chain reaction and sequence specific oligonucleotide probe method. Increased frequency of HLA-DQB1*050301 was observed in HIV+PTB- [p = 0.024, Odds Ratio (OR) 2.30, 95% Confidence Interval (CI) 1.11-4.90] and HIV+PTB+ patients (p = 0.044, OR 2.41, 95% CI 1.01-5.73) compared to healthy controls, suggesting that DQB1*050301 may be associated with susceptibility to HIV infection as well as development of PTB in HIV patients. Underrepresentation of HLA-DPB1*1501 was observed in HIV-PTB+ (p = 0.002, Pc = 0.034) and HIV+PTB+ (p = 0.036) patients compared to healthy controls, suggesting that DPB1*1501 may be associated with protection against PTB development both in HIV positive and negative subjects. Analysis on the amino acid variation in the peptide binding pocket at beta69 position of HLA-DPB1 molecules revealed that the beta69 arginine containing HLA-DPB1 alleles and the genotype lysine/arginine were underrepresented in HIV-PTB+ (allele: p = 0.003, Pc = 0.009; genotype: p = 0.0002, Pc = 0.001) and HIV+PTB+ (allele: p = 0.016, Pc = 0.048; genotype: p = 0.026). This suggests that HLA-DPB1 alleles with arginine may be associated with protection against development of PTB in both HIV infected as well as uninfected individuals. Further, the haplotypes HLA-DRB1*1502-DPB1*0201 and HLA-DQB1*0601-DPB1*0201 (Pc < 0.001) and HLA-DRB1*1502-DQB1*0601-DPB1*0201 (p = 0.006, OR 5.09, 95% CI 1.42-22.66) were significantly overrepresented in HIV+PTB+ patients compared to healthy controls suggesting that genetic susceptibility to PTB development in HIV patients may be modulated by interplay between HLA class II alleles, besides HLA class I alleles.
Selvaraj
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P
Tuberculosis Research Centre, Indian Council of Medical Research, Mayor V.R. Ramanathan Road, Chetput, Chennai 600031, India. p.selvaraj53@yahoo.com
Raghavan
S
S
Swaminathan
S
S
Alagarasu
K
K
Narendran
G
G
Narayanan
P R
PR
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000453:epidemiology / Q000235:genetics
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen