Major histocompatibility complex class II transactivator gene polymorphism: associations with Loefgren's syndrome

• Published in: Tissue antigens Vol. 76; no. 2; pp. 96 - 101
• Main Authors: Grunewald, J, Idali, F, Kockum, I, Seddighzadeh, M, Nisell, M, Eklund, A, Padyukov, L
• Format: Journal Article
• Language: English
• Published: 01.08.2010
• ISSN: 0001-2815
• DOI: 10.1111/j.1399-0039.2010.01476.x

The major histocompatibility complex (MHC) class II transactivator (MHC2TA) is known as a master regulator for expression of MHC class II molecules. In the present study, we investigated the influence on the risk for sarcoidosis of two variants of the MHC2TA gene, selected from previous association studies of inflammatory diseases. Seven hundred and twenty-eight sarcoidosis patients and 873 controls matched by ethnicity were included in the study. Patients were classified as with Loefgren's syndrome (or not) as subphenotypes. Individuals were genotyped for two single nucleotide polymorphisms (SNPs) of the MHC2TA gene, rs3087456 A/G and rs11074932 C/T, and were human leukocyte antigen (HLA)-DRB1-typed. After correction for multiple testing, our data showed a significant association with Loefgren's syndrome in allelic model for the rs3087456 SNP, which was not detected in non-Loefgren's patients. A similar trend was noted for the rs11074932 SNP. These risk factors were independent of HLA-DRB1*03, which is known to be associated with Loefgren's syndrome. The finding of a new genetic association between Loefgren's syndrome and MHC2TA gene polymorphisms, which seems independent of HLA-DRB1*03 and relates to the expression of MHC class II molecules, strongly supports the idea that Loefgren's syndrome is a separate disease entity.