caa a22 4500 467907307 CHVBK 20180406152838.0 cr unu---uuuuu 170328e20060601xx s 000 0 eng 10.1007/s00251-006-0120-7 doi (NATIONALLICENCE)springer-10.1007/s00251-006-0120-7 Functional impact of IgA nephropathy-associated selectin gene haplotype on leukocyte-endothelial interaction [Elektronische Daten] [Takashi Takei, Megumi Hiraoka, Kosaku Nitta, Keiko Uchida, Michiyo Deushi, Tao Yu, Noriko Nitta, Ken Tsuchiya, Wako Yumura, Hiroshi Nihei, Yusuke Nakamura, Masayuki Yoshida] Previously, we discovered single-nucleotide polymorphisms (SNPs) associated with Immunoglobulin A (IgA) nephropathy in selectin genes, which were 712C>T(P238S) in L selectin, -642A>G in the promoter region of L selectin, and 1402C>T(H468Y) in E selectin. Interestingly, these SNPs were in nearly complete linkage disequilibrium, thus two haplotypes, disease-associated TGT and wild-type (Wt) CAC, were constructed. To investigate the functional significance of TGT haplotype, a stable CHO transfectant expressing a P238S-L-selectin variant (CHO-varL) and a recombinant adenovirus vector containing an H468Y-E-selectin variant (Ad-varE) were established and compared to their Wt counterparts. Under flow, CHO-varL exhibited significantly less adhesion over IL-1β-activated HUVEC monolayers compared to CHO-wtL. Furthermore, a luciferase reporter construct, containing a promoter region of the L-selectin variant (luc-varL), exhibited significantly less transcription activity compared to Wt (luc-wtL). These results suggest that the adhesive interactions and expression level of L selectin in disease-associated haplotypes are significantly compromised, indicating a potential role of these SNPs in the pathogenesis of inflammatory diseases, including IgA nephropathy. Springer-Verlag, 2006 SNPs nationallicence Haplotype nationallicence Selectins nationallicence Adhesion assay nationallicence Luciferase activity nationallicence Takei Takashi Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut Hiraoka Megumi Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut Nitta Kosaku Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut Uchida Keiko Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut Deushi Michiyo Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut Yu Tao Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut Nitta Noriko Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut Tsuchiya Ken Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut Yumura Wako Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut Nihei Hiroshi Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut Nakamura Yusuke Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan aut Yoshida Masayuki Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut Immunogenetics Springer-Verlag 58/5-6(2006-06-01), 355-361 0093-7711 58:5-6<355 2006 58 251 https://doi.org/10.1007/s00251-006-0120-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-006-0120-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takei Takashi Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut NATIONALLICENCE 700 1- Hiraoka Megumi Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut NATIONALLICENCE 700 1- Nitta Kosaku Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut NATIONALLICENCE 700 1- Uchida Keiko Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut NATIONALLICENCE 700 1- Deushi Michiyo Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut NATIONALLICENCE 700 1- Yu Tao Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut NATIONALLICENCE 700 1- Nitta Noriko Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut NATIONALLICENCE 700 1- Tsuchiya Ken Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut NATIONALLICENCE 700 1- Yumura Wako Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut NATIONALLICENCE 700 1- Nihei Hiroshi Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan aut NATIONALLICENCE 700 1- Nakamura Yusuke Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan aut NATIONALLICENCE 700 1- Yoshida Masayuki Vascular Medicine and Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 D-809 Yushima, 113-8519, Bunkyo-ku, Tokyo, Japan aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 58/5-6(2006-06-01), 355-361 0093-7711 58:5-6<355 2006 58 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer