Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: critical evaluation of an association with HLA-DR3.

Abstract

Previous studies of sporadic inclusion body myositis (sIBM) have shown a strong association with HLA-DR3 and other components of the 8.1 ancestral haplotype (AH) (HLA-A1, B8, DR3), where the susceptibility locus has been mapped to the central major histocompatibility complex (MHC) region between HLA-DR and C4. Here, the association with HLA-DR3 and other genes in the central MHC and class II region was further investigated in a group of 42 sIBM patients and in an ethnically similar control group (n = 214), using single-nucleotide polymorphisms and microsatellite screening. HLA-DR3 (marking DRB1*0301 in Caucasians) was associated with sIBM (Fisher's test). However, among HLA-DR3-positive patients and controls, carriage of HLA-DR3 without microsatellite and single-nucleotide polymorphism alleles of the 8.1AH (HLA-A1, B8, DRB3*0101, DRB1*0301, DQB1*0201) was marginally less common in patients. Patients showed no increase in carriage of the 18.2AH (HLA-A30, B18, DRB3*0202, DRB1*0301, DQB1*0201) or HLA-DR3 without the central MHC of the 8.1AH, further arguing against HLA-DRB1 as the direct cause of susceptibility. Genes between HLA-DRB1 and HOX12 require further investigation. BTL-II lies in this region and is expressed in muscle. Carriage of allele 2 (exon 6) was more common in patients. BTL-II(E6)*2 is characteristic of the 35.2AH (HLA-A3, B35, DRB1*01) in Caucasians and HLA-DR1, BTL-II(E6)*2, HOX12*2, RAGE*2 was carried by several patients. The 8.1AH and 35.2AH may confer susceptibility to sIBM independently or share a critical allele.

• Authors: P Price, L Santoso, F Mastaglia, M Garlepp, C C Kok, R Allcock, N Laing
• Journal: Tissue antigens (Tissue Antigens) Vol. 64 Issue 5 Pg. 575-80 (Nov 2004) ISSN: 0001-2815 [Print] England
• PMID: 15496200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BTNL2 protein, human
• Butyrophilins
• HLA-B8 Antigen
• HLA-DR3 Antigen
• Membrane Glycoproteins

Topics

• Butyrophilins
• Genetic Predisposition to Disease
• HLA-B8 Antigen (genetics, immunology)
• HLA-DR3 Antigen (genetics, immunology)
• Haplotypes (genetics, immunology)
• Humans
• Major Histocompatibility Complex (genetics, immunology)
• Membrane Glycoproteins (genetics, immunology)
• Myositis, Inclusion Body (genetics, immunology)