Association of ANXA11 genetic variation with sarcoidosis in African Americans and European Americans

• DOI: 10.1038/gene.2012.48
• Publication Date: 2012-11-15T10:01:39Z
• Authors: A M Levin; M C Iannuzzi; C G Montgomery; S Trudeau; I Datta; P McKeigue; A Fischer; A Nebel; B A Rybicki
• Keywords: 0301 basic medicine; Sarcoidosis; Annexins; Genome, Human; Polymorphism, Single Nucleotide; White People; Black or African American; 03 medical and health sciences; HLA Antigens; Case-Control Studies; Humans; Promoter Regions, Genetic; Genetic Association Studies

A recent genome-wide association study in a German population and two subsequent studies in European populations found that a non-synonymous single-nucleotide polymorphism (SNP), rs1049550, within the annexin A11 (ANXA11) gene was associated with susceptibility to sarcoidosis. We sought to identify additional ANXA11 variants independently associated with sarcoidosis, determine whether any sarcoidosis-associated ANXA11 variants were associated with chest radiographic phenotypes, and explore human leukocyte antigen (HLA) SNP-SNP interactions with ANXA11. A total of 209 SNPs spanning 100 kb including the 5' promoter, coding, and 3' untranslated regions of ANXA11 were genotyped for 1689 sarcoidosis cases and 1252 controls. After adjustment for rs1049550, two additional novel ANXA11 sarcoidosis associations were identified only in African Americans--rs61860052 (odds ratio (OR)=0.62; 95% confidence interval (CI)=0.40-0.97) and rs4377299 (OR=1.31; 95% CI=1.06-1.63). These associations were more pronounced in radiologically-classified Scadding stage IV sarcoidosis cases. We also identified a significant SNP-SNP interaction between rs1049550 and a sarcoidosis risk SNP (rs9268839) near the HLA-DRA locus. This further genetic dissection of ANXA11 may provide additional insight into the immune dysregulation characteristic of sarcoidosis pathophysiology.