Association of erosive hand osteoarthritis with a single nucleotide polymorphism on the gene encoding interleukin-1 beta.
Association of erosive hand osteoarthritis with a single nucleotide polymorphism on the gene encoding interleukin-1 beta.
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DOI：
10.1016/s1063-4584(03)00054-2
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发表时间：
2003-06
影响因子：
7
通讯作者：
A. G. Stern;M. de Carvalho;G. Buck;R. Adler;T. Rao;D. Disler;G. Moxley
中科院分区：
文献类型：
--
作者：
A. G. Stern;M. de Carvalho;G. Buck;R. Adler;T. Rao;D. Disler;G. Moxley
某些形式的原发性骨关节炎（OA），特别是影响手关节的那些，具有遗传成分。最近的研究表明手和膝关节OA与人类染色体2 q上的白细胞介素-1（IL-1）区域相关。这项研究进行了评估的关联原发性OA的手（手OA）与IL-1 region marker.MethodsSixty-eight US Caucasoid的情况下，51名美国高加索人控制年龄在60岁或以上，从美国大西洋中部地区招募。根据美国风湿病学会（ACR）临床标准对手部OA进行分类，并对病例进行X线检查以进行亚组。对先前描述的IL-1α（由IL 1A编码）、IL-1β（IL 1B）和IL-1受体拮抗剂（IL 1 RN）基因的7个单核苷酸多态性（SNP）以及IL 1 RN可变串联重复序列（VNTR）标记进行基因分型。结果IL 1B 5810 G>A SNP基因型在非糜烂型和糜烂型手OA中均不处于Hardy-Weinberg平衡（p<0.05）。在糜烂性手OA亚组中发现了与IL 1B 5810 AA基因型的统计学显著相关性（相对风险3.8，p=0.007）。IL 1B 5810 AA基因型关联在糜烂性和非糜烂性手OA受试者之间也是显著的（相对风险4.01，p=0.008）。正如预期的那样，在IL 1B 5810 SNP和IL 1A（-）889 SNP、其他IL 1B SNP和最近的IL 1 RN SNP之间存在显著的连锁不平衡。IL 1B 5810 A等位基因最常出现在具有SNP等位基因IL 1B 1423 C、IL 1B 1903 T、IL 1B 5887 C和IL 1A（−）889 C的单倍型上。基因型在null位点未能显示证据表明人口分层，可能占虚假association.ConclusionStatistical证据显示侵蚀性手OA和基因组区域包含IL 1B 5810 SNP在美国高加索人群之间的关联。这支持了IL-1在手部OA严重表型发病机制中的潜在作用。
ObjectiveCertain forms of primary osteoarthritis (OA), particularly those affecting hand joints, have a genetic component. Recent studies have shown suggestive evidence that hand and knee OA are linked with the interleukin-1 (IL-1) region on human chromosome 2q. This study was undertaken to assess the association of primary OA of the hand (hand OA) with IL-1 region markers.MethodsSixty-eight US Caucasoid cases and 51 US Caucasoid controls aged 60 years or older were recruited from the Mid-Atlantic region of the United States. Hand OA was classified by American College of Rheumatology (ACR) Clinical Criteria, and cases were subjected to radiographic examination for subgrouping. Genotyping was done for seven previously described single nucleotide polymorphisms (SNPs) of genes for IL-1α (encoded by IL1A), IL-1β (IL1B), and the IL-1 receptor antagonist (IL1RN), as well as an IL1RN variable number of tandem repeat (VNTR) marker. Six microsatellite markers on other chromosomes (null loci) were also typed.ResultsThe IL1B 5810 G>A SNP genotypes marker were not in Hardy–Weinberg equilibrium (p<0.05 in both non-erosive and erosive hand OA subgroups). Statistically significant association with the IL1B 5810 AA genotype was found in the erosive hand OA subgroup (relative risk 3.8, p=0.007). This IL1B 5810 AA genotype association was also significant between erosive and non-erosive hand OA subjects (relative risk 4.01, p=0.008). As expected, significant linkage disequilibrium was present between IL1B 5810 SNP and IL1A (−)889 SNP, other IL1B SNPs, and the nearest IL1RN SNP examined. The IL1B 5810A allele occurs most frequently on haplotypes with the SNP alleles IL1B 1423C, IL1B 1903T, IL1B 5887C, and IL1A (−)889C. Genotypes at null loci failed to show evidence suggesting population stratification that might account for spurious association.ConclusionStatistical evidence shows association between erosive hand OA and a genomic region containing the IL1B 5810 SNP in a US Caucasoid population. This supports a potential role for IL-1 in the pathogenesis of a severe phenotype of hand OA.