Background and aim of the study: Rheumatic heart disease (RHD) is widespread in Pakistan. Specific alleles of the human leukocyte antigen (HLA) system are associated with RHD in various world populations. The study aim was to investigate the involvement of HLA class II alleles in genetic susceptibility to RHD in patients with relatively homogeneous clinical manifestations, in Pakistan.
Methods: Blood samples were collected from 114 unrelated patients (94 females, 20 males) with rheumatic mitral valve disease, predominantly mitral stenosis, as assessed by echocardiography. The control group comprised 109 unrelated, ethnically matched, healthy individuals (60 females, 49 males) with normal echocardiograms. Genomic DNA was extracted from venous blood using a standard phenol/chloroform extraction procedure. HLA-DRB, -DQA1, and -DQB1 alleles were typed using polymerase chain reaction with sequence-specific primers. HLA allele and haplotypes frequencies were then calculated.

Results: A significantly higher frequency of DRB1*07 was observed in patients as compared to controls (one-way parametric analysis of variance, F = 4.84, p = 0.028; OR = 1.76, p = 0.039). No alleles for the HLA-DQA1 or -DQB1 loci were associated with the disease. HLA-DRB1*07-DQA1*0501-DQB1*02, the only haplotype that differed significantly between patients and controls (one-way parametric Anova, F = 4.866, p = 0.028; OR = 7.33, p = 0.06), did not exhibit significant linkage disequilibrium.
Conclusion: These results show that HLA-DRB1*07, associated with RHD in various world populations, is also associated with RHD in the Pakistani population. The validation of HLA associations with RHD, which is observed in different world populations, may lead to the development of a cost-effective strategy in the primary prevention of this disease.



The Journal of Heart Valve Disease 2007;16:300-304