Susceptible and protective associations of HLA DRB1*/DQB1* alleles and haplotypes with ischaemic stroke.
Stroke has emerged as the second commonest cause of mortality worldwide and is a major public health problem. For the first time, we present here the association of human leucocyte antigen (HLA)-DRB1*/DQB1* alleles and haplotypes with ischaemic stroke in South Indian patients. Ischaemic stroke (IS) cases and controls were genotyped for HLA-DRB1*/DQB1* alleles by polymerase chain reaction sequence-specific primers (PCR-SSP) method. The frequencies of HLA class II alleles such as DRB1*04, DRB1*07, DRB1*11, DRB1*12, DRB1*13, DQB1*02 and DQB1*07 were high in IS patients than in the age- and gender-matched controls, suggesting that the individuals with these alleles are susceptible to ischaemic stroke in South India. The frequencies of alleles such as DRB1*03, DRB1*10, DRB1*14, DQB1*04 and DQB1*05 were less in IS cases than in the controls, suggesting a protective association. Haplotypes DRB1*04-DQB1*0301, DRB1*07-DQB1*02, DRB1*07-DQB1*0301, DRB1*11-DQB1*0301 and DRB1*13-DQB1*06 were found to be high in IS patients conferring susceptibility. The frequency of haplotype DRB1*10-DQB1*05 was high in controls conferring protection. IS-LVD and gender-stratified analysis too confirmed these susceptible and protective associations. Thus, HLA-DRB1*/DQB1* alleles and haplotypes strongly predispose South Indian population to ischaemic stroke. Further studies in different populations with large sample size or the meta-analysis are needed to explain the exact mechanism of associations of HLA gene(s) with IS.
Department of Biotechnology & Genetic Engineering, School of Biotechnology, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.
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Murali
Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
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Rathika
Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
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Ramgopal
Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
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Padma Malini
Hannah Joseph Hospital, Madurai, Tamil Nadu, India.
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Arun Kumar
Neethi Arasu Neuro Hospital, Madurai, Tamil Nadu, India.
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Neethi Arasu
Narayana Health, Bangalore, Karnataka, India.
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Jeyaram Illiayaraja
Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamil Nadu, India.
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Balakrishnan
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology
D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains