G.P.63 High-resolution analysis of HLA-DRB1 alleles and diplotypes in an Australian inclusion body myositis cohort
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- 作者：A. Rojana-udomsart ; A. Castley ; I. James ; M. Needham ; A. Scott ; T. Day ; L. Kiers ; A. Corbett ; C. Sue ; P. Martinez ; F. Christiansen ; F.L. Mastaglia
- 刊名：Neuromuscular Disorders
- 出版年：2012
- 出版时间：October, 2012
- 年：2012
- 卷：22
- 期：9-10
- 页码：853-854
- 全文大小：58 K
文摘
In Caucasians, susceptibility to sporadic inclusion body myositis (s-IBM) is associated with the HLA-DR3 serotype and the HLA-DRB1?0301 allele which encodes it, and with the extended 8.1 MHC ancestral haplotype. Most previous HLA studies in s-IBM have used serological typing or low-resolution (2-digit) genotyping to identify disease-associated alleles, and the contribution of alleles other than HLA-DRB1?0301 and of the complementary in trans allele at the HLA-DRB1 locus has received little attention. In the present study we performed high-resolution (4-digit) HLA-DRB1 genotyping in an Australian cohort of 105 s-IBM patients and 189 controls from the Busselton Population Study and analysed risk-associated alleles and effects on age-at-onset (AAO) of the disease. Case-control logistic regression analysis showed that, apart from the strongly associated HLA-DRB1?0301 allele (OR 13.6), HLA-DRB1?0101 (OR 3.65) and HLA-DRB1?1301 (OR 3.31) are independent risk alleles. A number of other alleles, HLA-DRB1?0401, ?0404, ?0701, ?0901, ?1101 and ?1501 were reduced in frequency in s-IBM cases and may be protective. We evaluated the influence of allele combinations on disease risk and found that the strongest estimated risk is with the HLA-DRB1?0301/?0101 diplotype, while other allele combinations have diminishing risk effects. HLA-DRB1?0301 was associated with an AAO 4.3 years earlier than other alleles and DRB1?1301 with an AAO 4.5 years later, despite it being a risk factor. The findings indicate that the influence of HLA-DRB1 in s-IBM is complex, influencing both disease risk and AAO, and that allelic interactions at the HLA-DRB1 locus contribute to disease susceptibility.