John S, Marlow A, Hajeer A, Ollier W, Silman A, Worthington J
Arthritis and Rheumatism Council Epidemiology Research Unit, University of Manchester, UK.
J Rheumatol. 1997 Mar;24(3):452-7.
To determine if there is any evidence of linkage between the natural resistance associated macrophage protein gene, NRAMP1, and rheumatoid arthritis (RA).
Two dinucleotide markers, D2S1471, a highly polymorphic marker within 160 kb of NRAMP1, and a less polymorphic marker in the promoter region of NRAMP1, have been analyzed in 115 affected sib-pair RA families (35 with 2 parents, 18 with one parent) from the Arthritis and Rheumatism Council (ARC) National Repository and an additional 85 probands from the ARC National Twin Study and 96 controls. Individuals were typed for both markers by fluorescence based semiautomated polymerase chain reaction analysis.
No evidence of increased allele sharing in affected sib-pairs was obtained using identity by descent (IBD), identity by state, and maximum likelihood score (MLS) analysis for the whole data set. A significant increase in allele sharing was observed with marker D2S1471 (LOD 0.74; p 0.05) in the HLA discordant subgroup using IBD and MLS-IBD. No significant differences in allele frequencies were observed for any markers in the association study.
In a subset of sib-pairs that shared one or zero HLA haplotypes, LOD scores suggestive of linkage were observed. This suggests a role for NRAMP1 polymorphism in a subset of patients who do not possess HLA susceptibility alleles.
确定天然抗性相关巨噬细胞蛋白基因（NRAMP1）与类风湿关节炎（RA）之间是否存在连锁证据。
对来自关节炎与风湿病理事会（ARC）国家储存库的115个受累同胞对RA家系（35个有双亲，18个有单亲）以及ARC国家双胞胎研究中的另外85名先证者和96名对照，分析了两个二核苷酸标记，即NRAMP1基因160 kb内的一个高度多态性标记D2S1471，以及NRAMP1启动子区域的一个多态性较低的标记。通过基于荧光的半自动聚合酶链反应分析对个体进行这两个标记的分型。
对整个数据集使用基于家系的同一性（IBD）、状态同一性和最大似然分数（MLS）分析，未获得受累同胞对中等位基因共享增加的证据。在HLA不一致的亚组中，使用IBD和MLS-IBD分析时，标记D2S1471观察到等位基因共享显著增加（LOD 0.74；p 0.05）。在关联研究中，任何标记的等位基因频率均未观察到显著差异。
在共享一个或零个HLA单倍型的同胞对亚组中，观察到提示连锁的LOD分数。这表明NRAMP1多态性在一部分不具有HLA易感等位基因的患者中起作用。
