Susceptible and protective associations of HLA DRB1/DQB1 alleles and haplotypes with ischaemic stroke

• Published in: International journal of immunogenetics 2016-06, Vol.43 (3), p.159-165
• Main Authors: Murali, V., Rathika, C., Ramgopal, S., Padma Malini, R., Arun Kumar, M. J., Neethi Arasu, V., Jeyaram Illiayaraja, K., Balakrishnan, K.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Female; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; HLA-DQ beta-Chains - genetics; HLA-DRB1 Chains - genetics; Humans; India; Male; Middle Aged; Stroke - diagnostic imaging; Stroke - genetics; Stroke - pathology
• ISSN: 1744-3121; 1744-313X
• DOI: 10.1111/iji.12266

Summary 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.