HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies.
OBJECTIVE
To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM.


METHODS
Molecular genetic analyses of HLA-A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571).


RESULTS
In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti-Jo-1 autoantibodies shared the risk factor HLA-DRB1*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti-signal recognition particle (DQA1*0102) and anti-Mi-2 autoantibodies (DRB1*0302). DRB1*0302 and the European American-, anti-Mi-2-associated risk factor DRB1*0701 were found to share a 4-amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove.


CONCLUSIONS
These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene-environment interactions.
O'Hanlon
Terrance P
TP
National Institute of Environmental Health Sciences, Bethesda, Maryland 20892, USA. ohanlont@niehs.nih.gov
Rider
Lisa G
LG
Mamyrova
Gulnara
G
Targoff
Ira N
IN
Arnett
Frank C
FC
Reveille
John D
JD
Carrington
Mary
M
Gao
Xiaojiang
X
Oddis
Chester V
CV
Morel
Penelope A
PA
Malley
James D
JD
Malley
Karen
K
Shamim
Ejaz A
EA
Chanock
Stephen J
SJ
Foster
Charles B
CB
Bunch
Thomas
T
Reed
Ann M
AM
Love
Lori A
LA
Miller
Frederick W
FW
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics* / Q000706:statistics & numerical data; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics; D002648:Child; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006643:Histidine-tRNA Ligase / Q000737:chemistry / Q000235:genetics; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009220:Myositis / Q000208:ethnology* / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D012307:Risk Factors; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
D001323:Autoantibodies; D001324:Autoantigens; C115323:CHD4 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D006643:Histidine-tRNA Ligase