PTPN22 and rheumatoid arthritis: gratifying replication.
PTPN22 and rheumatoid arthritis: gratifying replication.
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DOI：
10.1002/art.21125
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发表时间：
2005-07
影响因子：
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通讯作者：
P. Gregersen;F. Batliwalla
中科院分区：
文献类型：
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作者：
P. Gregersen;F. Batliwalla
《关节炎与风湿病》杂志（1,2）上的两篇文章提供了类风湿关节炎（RA）与位于PTPN22编码区功能多态性之间关联的关键证实，PTPN22编码细胞内蛋白酪氨酸磷酸酶非受体22 （PTPN22，也称为Lyp，一种淋巴细胞特异性磷酸酶）。这一观察结果现在被认为是HLA区域以外与类风湿关节炎最可靠和可重复的遗传关联。特别令人满意的是，PTPN22 620W变体除了RA外还易患多种其他自身免疫性疾病，这有力地支持了这些疾病背后的共同机制和共同分子途径的观点。最重要的是，这一发现显然是有用的，因为它提出了许多有趣的问题。我们对PTPN22的功能有了足够的了解，可以立即开展丰富多样的新实验方法，包括生物化学、细胞生物学、动物疾病模型、群体遗传学和流行病学。就PTPN22和人类自身免疫性疾病而言，2004年显然是一个里程碑。2004年3月，Bottini等人(3)使用候选基因方法报道，PTPN22核苷酸1858处的小等位基因(T)使美国和意大利人群易患1型糖尿病。这种多态性导致PTPN22蛋白密码子620处色氨酸(W)取代精氨酸(R)。独立工作，并结合广泛的功能单核苷酸多态性的指导下，以前
Two articles in this issue of Arthritis & Rheumatism (1, 2) provide critical confirmation of the association between rheumatoid arthritis (RA) and a functional polymorphism located in the coding region of PTPN22, the gene that encodes the intracellular protein tyrosine phosphatase nonreceptor 22 (PTPN22; also known as Lyp, a lymphoid-specific phosphatase). This observation now stands as the most robust and reproducible genetic association with RA outside of the HLA region. It is especially satisfying that the PTPN22 620W variant also predisposes to a variety of other autoimmune disorders in addition to RA, lending strong support to the opinion that common mechanisms and common molecular pathways underlie these disorders. What is most important is that this discovery is clearly useful in the sense that it raises a host of intriguing questions. We know just enough about the function of PTPN22 to proceed immediately with a rich variety of new experimental approaches that will encompass biochemistry, cell biology, animal disease models, population genetics, and epidemiology.The year 2004 was clearly a landmark in terms of PTPN22 and human autoimmune disease. In March 2004, using a candidate gene approach, Bottini et al (3) reported that the minor allele (T) at nucleotide 1858 of PTPN22 confers a predisposition to type 1 diabetes in US and Italian populations. This polymorphism results in a substitution of tryptophan (W) for arginine (R) at codon 620 of the PTPN22 protein. Working independently and combining a broad screen of functional single-nucleotide polymorphisms guided by previously