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

Authors

Emmy Okello, Makerere University
Andrea Z. Beaton, George Washington UniversityFollow
Charles Mondo, Uganda Heart Institute, Kampala, Uganda
Paul Kruszka, National Institutes of Health, Bethesda, MD
Noah Kiwanuka, Makerere University
Richard Odoi-Adome, Makerere University
Juergen Freers, Makerere University

Document Type

Journal Article

Publication Date

2014

Journal

BMC Cardiovascular Disorders

Volume

Volume 14

Inclusive Pages

Article number 28

Abstract

Background

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.

Methods

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.

Results

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 (P_C) = 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.

Conclusion

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.

Comments

Reproduced with permission of BioMed Central Cardiovascular Disorders.

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

APA Citation

Okello, E., Beaton, A.Z., Mondo, C.K., Kruszka, P., Kiwanuka, P. et al. (2014). Rheumatic heart disease in Uganda: the association between MHC class II HLA DR alleles and disease: a case control study. BMC Cardiovascular Disorders, 14:28.

Peer Reviewed

1

Open Access

1