Susceptible and protective associations ofHLA DRB1*/DQB1* alleles and haplotypes with ischaemic stroke

Abstract

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.

Association between human leucocyte antigen alleles and risk of stroke in Iranian population

“…Notably, we demonstrated HLA haplotypes A*24~B*07~DRB1*11, A*01~B*52~DRB1*15, A*24~B*35~DRB1*11 and A*02~B*51~DRB1*11 as risk haplotypes for stroke, while A*26~B*38~DRB1*11 and A*03~B*35~DRB1*04 had protective roles against stroke. Previous studies have shown haplotypes containing DRB1*11 allele as risk haplotypes for ischaemic stroke in different populations (Chen et al, ; Murali et al, ). However, DRB1*04 allele and haplotypes containing this allele have been previously associated with risk of ischaemic stroke in other populations (Liu et al, ; Murali et al, ).…”

“…Previous studies have shown haplotypes containing DRB1*11 allele as risk haplotypes for ischaemic stroke in different populations (Chen et al, ; Murali et al, ). However, DRB1*04 allele and haplotypes containing this allele have been previously associated with risk of ischaemic stroke in other populations (Liu et al, ; Murali et al, ). Consequently, our data reveal presence of an ethnic‐based background for contribution of HLA alleles and haplotypes in stroke risk.…”

“…A previous pilot study of human exome data has shown strong association between HLA‐DPB1 alleles and risk of ischaemic stroke (Cole et al, ). More recently, HLA‐DQB1 alleles have been reported as susceptibility alleles for ischaemic stroke in South Indian population (Murali et al, ). So, we suggest genotyping of whole HLA region to explore the role of other HLA variants and haplotypes in ischaemic stroke.…”

Apolipoprotein E polymorphisms are associated with ischemic stroke susceptibility in a Northwest China Han population

“…As a complex heterogeneous disease of multiple etiologies and major clinical manifestations, IS not only associated with kinds of traditional risk factors but also influenced by the gene polymorphisms [ 4 ]. Therefore, many candidate genes which may be related to IS, for example Apolipoprotein E ( APOE ), methylenetetrahydrofolate reductase ( MTHFR ), histone deacetylase 9 ( HDAC9 ), human leukocyte antigen ( HLA ) and so on, have been studied by researchers [ 5 – 8 ].…”

Peripheral biomarkers of stroke: Focus on circulatory microRNAs

“…In the recent years, hundreds of genes were examined and it may have an impact on stroke pathogenesis or genes that are associated with clinical risk factors such as hypertension, diabetes, hyperlipidemia and vascular disease [14-16]. But only a few were fully proven to influence the susceptibility to the disease and have generated negative or conflicting results.…”