Association of the truncating splice site mutation in BTNL2 with multiple sclerosis is secondary to HLA-DRB1*15.
Association of the truncating splice site mutation in BTNL2 with multiple sclerosis is secondary to HLA-DRB1*15.
复制标题
BTNL2 中的截短剪接位点突变与多发性硬化症的关联继发于 HLA-DRB1*15。
DOI：
10.1093/hmg/ddi436
复制
发表时间：
2006
影响因子：
3.5
通讯作者：
Trowsdale,John
中科院分区：
文献类型：
--
作者：
Traherne,JamesA;Barcellos,LisaF;Sawcer,StephenJ;Compston,Alastair;Ramsay,PatriciaP;Hauser,StephenL;Oksenberg,JorgeR;Trowsdale,John
The major histocompatibility complex human leukocyte antigen (HLA)-DRB1*15(DR2) haplotype is strongly associated with risk of multiple sclerosis (MS). The primary susceptibility has been localized to only ∼200 kb encompassing theHLA-DRand-DQloci. Further dissection of disease association with this region is demanding because of the high levels of linkage disequilibrium (LD). Recently, evidence was obtained for the involvement of a gene, potentially encoding an immune co-receptor, in anotherDR2-associated inflammatory condition, sarcoidosis. The implicated gene,BTNL2, is adjacent toDRand is in strong LD withHLA-DRB1. This fact, combined with a sequence relationship betweenBTNL2and myelin oligodendrocyte glycoprotein, an autoantigen associated with MS, makes the gene an attractive candidate. To determine whetherBTNL2contributes to MS, we genotyped 1136 well-characterized MS families from the UK and the USA, as well as an African-American case–control data set, making this among the largest genetic studies in MS. Family-based and case–control association studies were performed for theBTNL2andHLA-DRB1loci. In all family data sets, the protein-truncating allele ofBTNL2, implicated in sarcoidosis, was significantly over-transmitted to cases (combined data sets: globalP=2.4×10−11). Given that the protein-truncating allele ofBTNL2virtually always occurred withDRB1*15, an effect could only be tested inDRB1*15-negative individuals or pedigrees. However, despite adequate power to detect an independent association, no difference in transmission ofBTNL2alleles or genotypes was observed inDRB1*15-negative individuals with MS. Conditional logistic regression modeling also strongly supported the conclusion thatBTNL2does not confer additional disease risk. The association ofBTNL2with MS observed in the African-American data set was also secondary to the primaryDRB1*15association.
