National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit, Botnar Research Centre, Oxford, UK.
Clin Exp Rheumatol. 2012 Jan-Feb;30(1):110-3. Epub 2012 Mar 7.
To replicate the possible genetic association between ankylosing spondylitis (AS) and TNFRSF1A.
TNFRSF1A was re-sequenced in 48 individuals with AS to identify novel polymorphisms. Nine single nucleotide polymorphisms (SNPs) in TNFRSF1A and 5 SNPs in the neighbouring gene SCNN1A were genotyped in 1604 UK Caucasian individuals with AS and 1019 matched controls. An extended study was implemented using additional genotype data on 8 of these SNPs from 1400 historical controls from the 1958 British Birth Cohort. A meta-analysis of previously published results was also undertaken.
One novel variant in intron 6 was identified but no new coding variants. No definite associations were seen in the initial study but in the extended study there were weak associations with rs4149576 (p=0.04) and rs4149577 (p=0.007). In the meta-analysis consistent, somewhat stronger associations were seen with rs4149577 (p=0.002) and rs4149578 (p=0.006).
These studies confirm the weak genetic associations between AS and TNFRSF1A. In view of the previously reported associations of TNFRSF1A with AS, in Caucasians and Chinese, and the biological plausibility of this candidate gene, replication of this finding in well powered studies is clearly indicated.
复制强直性脊柱炎（AS）与 TNFRSF1A 之间可能的遗传关联。
对 48 名 AS 患者进行 TNFRSF1A 重测序，以鉴定新的多态性。在 1604 名英国白种人 AS 患者和 1019 名匹配对照中，对 TNFRSF1A 中的 9 个单核苷酸多态性（SNP）和相邻基因 SCNN1A 中的 5 个 SNP 进行基因分型。利用来自 1958 年英国出生队列的 8 个 SNP 的额外基因型数据，进行了扩展研究。还对之前发表的结果进行了荟萃分析。
在 6 号内含子中发现了一个新的变体，但没有新的编码变体。在初始研究中未发现明确的关联，但在扩展研究中，rs4149576（p=0.04）和 rs4149577（p=0.007）与 rs4149576 存在弱关联。在荟萃分析中，rs4149577（p=0.002）和 rs4149578（p=0.006）的关联更为一致和强烈。
这些研究证实了 AS 与 TNFRSF1A 之间存在微弱的遗传关联。鉴于 TNFRSF1A 与 AS 的先前报道的关联，以及该候选基因在白种人和中国人中的生物学合理性，在具有良好效力的研究中复制这一发现是非常必要的。
