OBJECTIVES: This study used a meta-analysis to examine HLA-DR frequencies in rheumatic heart disease and prospectively examined other class II allelic disease associations. BACKGROUND: Studies of rheumatic heart disease have reported HLA class II allelic associations, but these are inconsistent. METHODS: A meta-analysis combined all known (n = 10) studies to determine disease risk associated with HLA-DR antigen expression. Meta-analysis of studies grouped by ethnic derivation of subjects was also performed. The present study also examined DQA, DQB and DPB allele frequencies by DNA-based strategies. RESULTS: Meta-analysis showed a significant negative disease association with DR5 (odds ratio [OR] 0.67, p < 0.00003) for all combined studies. Among black patients, DR1 was increased (OR 2.80, p < 0.004); DR6 was increased (OR, 2.03, p < 0.003); and DR 8 was decreased (OR 0.32, p < 0.02). Among Eastern Indian patients, DR3 was increased (OR 2.44, p < 0.00003), with decreased expression for DR2 (OR 0.31, p < 0.00001) and DR5 (OR 0.52, p < 0.05). DR4 was increased among American whites (OR 1.74, p < 0.03), although there was significant heterogeneity among studies of whites. DQA, DQB and DPB allele frequencies were similar for control subjects and patients. CONCLUSIONS: Our findings support an association between major histocompatibility complex class II alleles and risk for rheumatic heart disease. However, heterogeneity in associations was observed among different ethnic and racial groups; regional and temporal differences in streptococcal outbreaks may compound this heterogeneity. Further studies are necessary to elucidate the respective contributions of these variables.
OBJECTIVES: This study used a meta-analysis to examine HLA-DR frequencies in rheumatic heart disease and prospectively examined other class II allelic disease associations. BACKGROUND: Studies of rheumatic heart disease have reported HLA class II allelic associations, but these are inconsistent. METHODS: A meta-analysis combined all known (n = 10) studies to determine disease risk associated with HLA-DR antigen expression. Meta-analysis of studies grouped by ethnic derivation of subjects was also performed. The present study also examined DQA, DQB and DPB allele frequencies by DNA-based strategies. RESULTS: Meta-analysis showed a significant negative disease association with DR5 (odds ratio [OR] 0.67, p < 0.00003) for all combined studies. Among black patients, DR1 was increased (OR 2.80, p < 0.004); DR6 was increased (OR, 2.03, p < 0.003); and DR 8 was decreased (OR 0.32, p < 0.02). Among Eastern Indian patients, DR3 was increased (OR 2.44, p < 0.00003), with decreased expression for DR2 (OR 0.31, p < 0.00001) and DR5 (OR 0.52, p < 0.05). DR4 was increased among American whites (OR 1.74, p < 0.03), although there was significant heterogeneity among studies of whites. DQA, DQB and DPB allele frequencies were similar for control subjects and patients. CONCLUSIONS: Our findings support an association between major histocompatibility complex class II alleles and risk for rheumatic heart disease. However, heterogeneity in associations was observed among different ethnic and racial groups; regional and temporal differences in streptococcal outbreaks may compound this heterogeneity. Further studies are necessary to elucidate the respective contributions of these variables.
Authors: Emmy Okello; Andrea Beaton; Charles K Mondo; Paul Kruszka; Noah Kiwanuka; Richard Odoi-Adome; Juergen Freers Journal: BMC Cardiovasc Disord Date: 2014-02-28 Impact factor: 2.298