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Rheumatic heart disease in Uganda: the association between MHC class II HLA DR alleles and disease: a case control study

Emmy Okello12*, Andrea Beaton3, Charles K Mondo1, Paul Kruszka4, Noah Kiwanuka5, Richard Odoi-Adome6 and Juergen Freers1

Author Affiliations

1 Department of Medicine, Makerere University/Uganda Heart Institute, Ward 1C, Mulago Hospital Complex., PO Box 7051, Kampala, Uganda

2 Uganda Heart Institute, Mulago Hospital Complex, Kampala, Uganda

3 Department of Cardiology, Children’s National Medical Center, Washington, DC, USA

4 National Human Genome Research Institute/NIH, Bethesda, USA

5 Department of Epidemiology and Biostatistics, School of Public Health, Makerere University, Kampala, Uganda

6 School of Pharmacy, Makerere University, Kampala, Uganda

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BMC Cardiovascular Disorders 2014, 14:28  doi:10.1186/1471-2261-14-28

Published: 28 February 2014



Rheumatic heart disease (RHD), the only long term consequence of acute rheumatic fever, remains a leading cause of morbidity and mortality among young adults in Uganda. An inherited susceptibility to acute rheumatic fever centers around the major histocompatibility class II human leucocyte antigens. However, there is paucity of data from sub-Saharan Africa. This study compares the frequency of HLA class II DR alleles between RHD cases and normal controls in Uganda.


One hundred ninety-nine participants including 96 established RHD cases aged 5–60 years and 103 age and sex matched normal controls were recruited for participation. DNA was manually extracted from buffy coat samples and HLA analysis was performed. HLA-DR allelic frequency comparison between cases and controls were estimated using conditional logistic regression with 95% confidence intervals. P -values were corrected for multiple hypothesis testing.


199 participants (103 female, 51.8%) completed the study. The mean (SD) age in years for cases and controls were 29.6 (10.2) and 29(18), respectively. After conditional logistic regression and multiple hypothesis testing, HLA-DR1was associated with a decreased risk of RHD (OR = 0.42, CI 0.21-085, P = 0.01, Corrected P value (PC) = 0.09,) while HLA-DR11 was associated with increased risk of RHD (OR = 3.31, CI 1.57-6.97, P = <0.001, Pc < 0.001). No other significant associations were found.


In this first study of HLA genetic susceptibility to RHD in Uganda, HLA- DR1 was more common in normal controls while HLA- DR11 was more common among RHD cases suggesting a disease susceptibility association. In future studies, high resolution HLA analysis and genome wide studies should be carried out to confirm this pattern.

Rheumatic heart disease; HLA-DR1; HLA-DRB11; MHC- major histocompatibility complex