TY - JOUR
T1 - Genome-wide association study in asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus
AU - Yang, Wanling
AU - Shen, Nan
AU - Ye, Dong Qing
AU - Liu, Qiji
AU - Zhang, Yan
AU - Qian, Xiao Xia
AU - Hirankarn, Nattiya
AU - Ying, Dingge
AU - Pan, Hai Feng
AU - Mok, Chi Chiu
AU - Chan, Tak Mao
AU - Wong, Raymond Woon Sing
AU - Lee, Ka Wing
AU - Mok, Mo Yin
AU - Wong, Sik Nin
AU - Leung, Alexander Moon Ho
AU - Li, Xiang Pei
AU - Avihingsanon, Yingyos
AU - Wong, Chun Ming
AU - Lee, Tsz Leung
AU - Ho, Marco Hok Kung
AU - Lee, Pamela Pui Wah
AU - Chang, Yuk Kwan
AU - Li, Philip H.
AU - Li, Ruo Jie
AU - Zhang, Lu
AU - Wong, Wilfred Hing Sang
AU - Ng, Irene Oi Lin
AU - Lau, Chak Sing
AU - Sham, Pak Chung
AU - Lau, Yu Lung
PY - 2010/2
Y1 - 2010/2
N2 - Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33x10-11, OR = 1.29; WDFY4: rs7097397, P = 8.15x10-12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3'-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved.
AB - Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33x10-11, OR = 1.29; WDFY4: rs7097397, P = 8.15x10-12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3'-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved.
UR - https://www.scopus.com/pages/publications/77649206245
U2 - 10.1371/journal.pgen.1000841
DO - 10.1371/journal.pgen.1000841
M3 - 文章
C2 - 20169177
AN - SCOPUS:77649206245
SN - 1553-7390
VL - 6
JO - PLoS Genetics
JF - PLoS Genetics
IS - 2
M1 - e1000841
ER -
