Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0084770
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dc.titleFamilial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese
dc.contributor.authorMa R.C.W.
dc.contributor.authorLee H.M.
dc.contributor.authorLam V.K.L.
dc.contributor.authorTam C.H.T.
dc.contributor.authorHo J.S.K.
dc.contributor.authorZhao H.-L.
dc.contributor.authorGuan J.
dc.contributor.authorKong A.P.S.
dc.contributor.authorLau E.
dc.contributor.authorZhang G.
dc.contributor.authorLuk A.
dc.contributor.authorWang Y.
dc.contributor.authorTsui S.K.W.
dc.contributor.authorChan T.F.
dc.contributor.authorHu C.
dc.contributor.authorJia W.P.
dc.contributor.authorPark K.S.
dc.contributor.authorLee H.K.
dc.contributor.authorFuruta H.
dc.contributor.authorNanjo K.
dc.contributor.authorShyong Tai E.
dc.contributor.authorNg D.P.-K.
dc.contributor.authorTang N.L.S.
dc.contributor.authorWoo J.
dc.contributor.authorLeung P.C.
dc.contributor.authorXue H.
dc.contributor.authorWong J.
dc.contributor.authorLeung P.S.
dc.contributor.authorLau T.C.K.
dc.contributor.authorTong P.C.Y.
dc.contributor.authorXu G.
dc.contributor.authorNg M.C.Y.
dc.contributor.authorSo W.Y.
dc.contributor.authorChan J.C.N.
dc.date.accessioned2020-03-26T06:44:59Z
dc.date.available2020-03-26T06:44:59Z
dc.date.issued2014
dc.identifier.citationMa R.C.W., Lee H.M., Lam V.K.L., Tam C.H.T., Ho J.S.K., Zhao H.-L., Guan J., Kong A.P.S., Lau E., Zhang G., Luk A., Wang Y., Tsui S.K.W., Chan T.F., Hu C., Jia W.P., Park K.S., Lee H.K., Furuta H., Nanjo K., Shyong Tai E., Ng D.P.-K., Tang N.L.S., Woo J., Leung P.C., Xue H., Wong J., Leung P.S., Lau T.C.K., Tong P.C.Y., Xu G., Ng M.C.Y., So W.Y., Chan J.C.N. (2014). Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese. PLoS ONE 9 (1) : e84770. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0084770
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165964
dc.description.abstractIn Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57-3.96, P = 8.4 × 10-5). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02-1.12, P<inf>meta</inf> = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07-2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19-9.19, P = 0.0214) and 3.27(1.25-11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese. © 2014 Ma et al.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectinsulin
dc.subjectDACH1 protein, human
dc.subjecteye protein
dc.subjecttranscription factor
dc.subjectadult
dc.subjectarticle
dc.subjectAsian
dc.subjectautopsy
dc.subjectbioinformatics
dc.subjectcardiovascular disease
dc.subjectcase control study
dc.subjectChinese
dc.subjectcohort analysis
dc.subjectcontrolled study
dc.subjectcoronary artery atherosclerosis
dc.subjectDachshund homolog 1 gene
dc.subjectdiabetes mellitus
dc.subjectfamilial young onset diabetes mellitus
dc.subjectfemale
dc.subjectgene
dc.subjectgene expression
dc.subjectgenetic analysis
dc.subjectgenetic association
dc.subjectgenetic variability
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectimpaired glucose tolerance
dc.subjectinsulin release
dc.subjectinsulin resistance
dc.subjectintron
dc.subjectischemic heart disease
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmolecular pathology
dc.subjectnon insulin dependent diabetes mellitus
dc.subjectperipheral blood mononuclear cell
dc.subjectregulatory sequence
dc.subjectsingle nucleotide polymorphism
dc.subjectsystolic blood pressure
dc.subjectaged
dc.subjectAsian continental ancestry group
dc.subjectCardiovascular Diseases
dc.subjectDiabetes Mellitus, Type 2
dc.subjectgenetic predisposition
dc.subjectgenetics
dc.subjectgenotype
dc.subjectmiddle aged
dc.subjectPrediabetic State
dc.subjectsingle nucleotide polymorphism
dc.subjectAged
dc.subjectAsian Continental Ancestry Group
dc.subjectCardiovascular Diseases
dc.subjectCase-Control Studies
dc.subjectDiabetes Mellitus, Type 2
dc.subjectEye Proteins
dc.subjectFemale
dc.subjectGenetic Predisposition to Disease
dc.subjectGenome-Wide Association Study
dc.subjectGenotype
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectPolymorphism, Single Nucleotide
dc.subjectPrediabetic State
dc.subjectTranscription Factors
dc.typeArticle
dc.contributor.departmentSAW SWEE HOCK SCHOOL OF PUBLIC HEALTH
dc.description.doi10.1371/journal.pone.0084770
dc.description.sourcetitlePLoS ONE
dc.description.volume9
dc.description.issue1
dc.description.pagee84770
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