TY - JOUR
T1 - A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus
AU - The Italian Collaborative Group
AU - Orrú, Valeria
AU - Tsai, Sophia J.
AU - Rueda, Blanca
AU - Fiorillo, Edoardo
AU - Stanford, Stephanie M.
AU - Dasgupta, Jhimli
AU - Hartiala, Jaana
AU - Zhao, Lei
AU - Ortego-Centeno, Norberto
AU - D'Alfonso, Sandra
AU - Arnett, Frank C.
AU - Wu, Hui
AU - Gonzalez-Gay, Miguel A.
AU - Tsao, Betty P.
AU - Pons-Estel, Bernardo
AU - Alarcon-Riquelme, Marta E.
AU - He, Yantao
AU - Zhang, Zhong Yin
AU - Allayee, Hooman
AU - Chen, Xiaojiang S.
AU - Martin, Javier
AU - Bottini, Nunzio
AU - Danieli, Giovanna
AU - Galeazzi, Mauro
AU - Sabbadini, Maria Grazia
AU - Migliaresi, Sergio
AU - Sebastiani, Gian Domenico
PY - 2008/11/3
Y1 - 2008/11/3
N2 - A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.
AB - A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.
UR - http://www.scopus.com/inward/record.url?scp=58849120030&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddn363
DO - 10.1093/hmg/ddn363
M3 - Article
SN - 0964-6906
VL - 18
SP - 569
EP - 579
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 3
ER -