title: Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese.
abstract: Several previous linkage scans in type 2 diabetes (T2D) families indicated a putative susceptibility locus on chromosome 12q15-q22, while the underlying gene for T2D has not yet been identified. We performed a region-wide association analysis on 12q15-q22, using a dense set of >500 single-nucleotide polymorphisms (SNPs), in 1492 unrelated Japanese individuals enrolled in this study. We identified an association between T2D and a haplotype block spanning 13.6 kb of genomic DNA that includes the entire SOCS2 gene. Evolutionary-based haplotype analysis of haplotype-tagging SNPs followed by a "sliding window" haplotypic analysis indicated SNPs that mapped to the 5' region of the SOCS2gene to be associated with T2D with high statistical significance. The SOCS2 gene was expressed ubiquitously in human and murine tissues, including pancreatic beta-cell lines. Adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or isolated rat islets significantly suppressed glucose-stimulated insulin secretion. Our data indicate that SOCS2 may play a role in susceptibility to T2D in the Japanese.
authors.affiliation: Molecular Medicine Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kato
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nomura
authors.forename: Dai
authors.initials: D
authors.lastname: Osabe
authors.forename: Shuichi
authors.initials: S
authors.lastname: Shinohara
authors.forename: Osamu
authors.initials: O
authors.lastname: Mizumori
authors.forename: Rumi
authors.initials: R
authors.lastname: Katashima
authors.forename: Shoji
authors.initials: S
authors.lastname: Iwasaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishimura
authors.forename: Masayasu
authors.initials: M
authors.lastname: Yoshino
authors.forename: Masato
authors.initials: M
authors.lastname: Kobori
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Ichiishi
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Keshavarz
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kunika
authors.forename: Maki
authors.initials: M
authors.lastname: Moritani
authors.forename: Eiji
authors.initials: E
authors.lastname: Kudo
authors.forename: Kazue
authors.initials: K
authors.lastname: Tsugawa
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hamada
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yasui
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011863:Radioimmunoassay; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D007328:Insulin; C106643:SOCS2 protein, human; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D005947:Glucose