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Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects

DC Field Value Language
dc.contributor.author최홍식-
dc.contributor.author김미영-
dc.contributor.author김미영-
dc.date.accessioned2016-02-19T11:27:26Z-
dc.date.available2016-02-19T11:27:26Z-
dc.date.issued2001-
dc.identifier.issn0027-8424-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/143184-
dc.description.abstractMutations in several genes encoding transcription factors of the hepatocyte nuclear factor (HNF) cascade are associated with maturity-onset diabetes of the young (MODY), a monogenic form of early-onset diabetes mellitus. The ability of the orphan nuclear receptor small heterodimer partner (SHP, NR0B2) to modulate the transcriptional activity of MODY1 protein, the nuclear receptor HNF-4α, suggested SHP as a candidate MODY gene. We screened 173 unrelated Japanese subjects with early-onset diabetes for mutations in this gene and found five different mutations (H53fsdel10, L98fsdel9insAC, R34X, A195S, and R213C) in 6 subjects as well as one apparent polymorphism (R216H), all present in the heterozygous state. Interestingly, all of the subjects with the mutations were mildly or moderately obese at onset of diabetes, and analysis of the lineages of these individuals indicated that the SHP mutations were associated with obesity rather than with diabetes. Therefore, an additional group of 101 unrelated nondiabetic subjects with early-onset obesity was screened for mutations in the SHP gene. Two of the previously observed mutations (R34X and A195S) and two additional mutations (R57W and G189E) were identified in 6 subjects, whereas no mutations were identified in 116 young nondiabetic lean controls (P = 0.0094). Functional studies of the mutant proteins show that the mutations result in the loss of SHP activity. These results suggest that genetic variation in the SHP gene contributes to increased body weight and reveal a pathway leading to this common metabolic disorder in Japanese.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdolescent-
dc.subject.MESHAdult-
dc.subject.MESHAge of Onset-
dc.subject.MESHAmino Acid Substitution-
dc.subject.MESHBasic Helix-Loop-Helix Leucine Zipper Transcription Factors-
dc.subject.MESHBirth Weight/genetics-
dc.subject.MESHBody Weight/genetics-
dc.subject.MESHChild-
dc.subject.MESHChromosomes, Human, Pair 1/genetics-
dc.subject.MESHComorbidity-
dc.subject.MESHDNA Mutational Analysis-
dc.subject.MESHDNA-Binding Proteins*-
dc.subject.MESHDiabetes Mellitus, Type 2/epidemiology-
dc.subject.MESHDiabetes Mellitus, Type 2/ethnology-
dc.subject.MESHDiabetes Mellitus, Type 2/genetics*-
dc.subject.MESHFemale-
dc.subject.MESHGene Expression Regulation-
dc.subject.MESHGenes, Dominant-
dc.subject.MESHGenes, Recessive-
dc.subject.MESHGenetic Predisposition to Disease-
dc.subject.MESHHepatocyte Nuclear Factor 4-
dc.subject.MESHHeterozygote-
dc.subject.MESHHumans-
dc.subject.MESHHyperinsulinism/epidemiology-
dc.subject.MESHHyperinsulinism/ethnology-
dc.subject.MESHHyperinsulinism/genetics-
dc.subject.MESHJapan/epidemiology-
dc.subject.MESHLod Score-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutation, Missense-
dc.subject.MESHObesity/epidemiology-
dc.subject.MESHObesity/ethnology-
dc.subject.MESHObesity/genetics*-
dc.subject.MESHPedigree-
dc.subject.MESHPhosphoproteins/physiology-
dc.subject.MESHPoint Mutation-
dc.subject.MESHPolymorphism, Genetic-
dc.subject.MESHReceptors, Cytoplasmic and Nuclear/genetics*-
dc.subject.MESHTranscription Factors/physiology-
dc.subject.MESHTranscriptional Activation-
dc.subject.MESHTransfection-
dc.subject.MESHTumor Cells, Cultured-
dc.titleMutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Otorhinolaryngology (이비인후과학)-
dc.contributor.googleauthorHidekazu Nishigori-
dc.contributor.googleauthorHideaki Tomura-
dc.contributor.googleauthorNaoko Tonooka-
dc.contributor.googleauthorMasao Kanamori-
dc.contributor.googleauthorShirou Yamada-
dc.contributor.googleauthorKimie Sho-
dc.contributor.googleauthorIturo Inoue-
dc.contributor.googleauthorNobuyuki Kikuchi-
dc.contributor.googleauthorKazumichi Onigata-
dc.contributor.googleauthorItaru Kojima-
dc.contributor.googleauthorTomoko Kohama-
dc.contributor.googleauthorKazuya Yamagata-
dc.contributor.googleauthorQin Yang-
dc.contributor.googleauthorYuji Matsuzawa-
dc.contributor.googleauthorTakashi Miki-
dc.contributor.googleauthorSusumu Seino-
dc.contributor.googleauthorMi-Young Kim-
dc.contributor.googleauthorHueng-Sik Choi-
dc.contributor.googleauthorYoon-Kwang Lee-
dc.contributor.googleauthorDavid D. Moore-
dc.contributor.googleauthorJun Takeda-
dc.identifier.doi10.1073/pnas.98.2.575-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA04223-
dc.relation.journalcodeJ02550-
dc.identifier.eissn1091-6490-
dc.identifier.pmid11136233-
dc.contributor.alternativeNameChoi, Hong Shik-
dc.contributor.alternativeNameKim, Mi Young-
dc.contributor.affiliatedAuthorChoi, Hong Shik-
dc.rights.accessRightsfree-
dc.citation.volume98-
dc.citation.number2-
dc.citation.startPage575-
dc.citation.endPage580-
dc.identifier.bibliographicCitationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.98(2) : 575-580, 2001-
dc.identifier.rimsid39119-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers

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