Sökning: WFRF:(Brosnan Julia) > Segre Ayellet V. > Loss-of-function mu...
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000 | 07229naa a2201321 4500 | |
001 | oai:lup.lub.lu.se:04e31993-2f8c-4069-a74a-503f183912ae | |
003 | SwePub | |
008 | 160401s2014 | |||||||||||000 ||eng| | |
009 | oai:DiVA.org:uu-225085 | |
024 | 7 | a https://lup.lub.lu.se/record/43841982 URI |
024 | 7 | a https://doi.org/10.1038/ng.29152 DOI |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2250852 URI |
040 | a (SwePub)lud (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Flannick, Jason4 aut |
245 | 1 0 | a Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. |
264 | c 2014-03-02 | |
264 | 1 | b Springer Science and Business Media LLC,c 2014 |
520 | a Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
700 | 1 | a Thorleifsson, Gudmar4 aut |
700 | 1 | a Lind, Larsu Uppsala universitet,Kardiovaskulär epidemiologi4 aut0 (Swepub:uu)larslind |
700 | 1 | a Jacobs, Suzanne B R4 aut |
700 | 1 | a Grarup, Niels4 aut |
700 | 1 | a Burtt, Noël P4 aut |
700 | 1 | a Mahajan, Anubha4 aut |
700 | 1 | a Fuchsberger, Christian4 aut |
700 | 1 | a Atzmon, Gil4 aut |
700 | 1 | a Benediktsson, Rafn4 aut |
700 | 1 | a Blangero, John4 aut |
700 | 1 | a Bowden, Don W4 aut |
700 | 1 | a Brandslund, Ivan4 aut |
700 | 1 | a Brosnan, Julia4 aut |
700 | 1 | a Burslem, Frank4 aut |
700 | 1 | a Chambers, John4 aut |
700 | 1 | a Cho, Yoon Shin4 aut |
700 | 1 | a Christensen, Cramer4 aut |
700 | 1 | a Douglas, Desireeu Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Cellpatologi, Malmö,Celiac Disease and Diabetes Unit,Lund University Research Groups,Cell Pathology, Malmö4 aut0 (Swepub:lu)cob-ddo |
700 | 1 | a Duggirala, Ravindranath4 aut |
700 | 1 | a Dymek, Zachary4 aut |
700 | 1 | a Farjoun, Yossi4 aut |
700 | 1 | a Fennell, Timothy4 aut |
700 | 1 | a Fontanillas, Pierre4 aut |
700 | 1 | a Forsén, Tom4 aut |
700 | 1 | a Gabriel, Stacey4 aut |
700 | 1 | a Glaser, Benjamin4 aut |
700 | 1 | a Gudbjartsson, Daniel F4 aut |
700 | 1 | a Hanis, Craig4 aut |
700 | 1 | a Hansen, Torben4 aut |
700 | 1 | a Hreidarsson, Astradur B4 aut |
700 | 1 | a Hveem, Kristian4 aut |
700 | 1 | a Ingelsson, Eriku Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi4 aut0 (Swepub:uu)ering425 |
700 | 1 | a Isomaa, Bo4 aut |
700 | 1 | a Johansson, Stefan4 aut |
700 | 1 | a Jørgensen, Torben4 aut |
700 | 1 | a Jørgensen, Marit Eika4 aut |
700 | 1 | a Kathiresan, Sekar4 aut |
700 | 1 | a Kong, Augustine4 aut |
700 | 1 | a Kooner, Jaspal4 aut |
700 | 1 | a Kravic, Jasminau Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups4 aut0 (Swepub:lu)med-jik |
700 | 1 | a Laakso, Markku4 aut |
700 | 1 | a Lee, Jong-Young4 aut |
700 | 1 | a Lind, Lars4 aut |
700 | 1 | a Lindgren, Cecilia M4 aut |
700 | 1 | a Linneberg, Allan4 aut |
700 | 1 | a Masson, Gisli4 aut |
700 | 1 | a Meitinger, Thomas4 aut |
700 | 1 | a Mohlke, Karen L4 aut |
700 | 1 | a Molven, Anders4 aut |
700 | 1 | a Morris, Andrew P4 aut |
700 | 1 | a Potluri, Shobha4 aut |
700 | 1 | a Rauramaa, Rainer4 aut |
700 | 1 | a Ribel-Madsen, Rasmus4 aut |
700 | 1 | a Richard, Ann-Marie4 aut |
700 | 1 | a Rolph, Tim4 aut |
700 | 1 | a Salomaa, Veikko4 aut |
700 | 1 | a Segrè, Ayellet V4 aut |
700 | 1 | a Skärstrand, Hannau Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups4 aut0 (Swepub:lu)med-hsk |
700 | 1 | a Steinthorsdottir, Valgerdur4 aut |
700 | 1 | a Stringham, Heather M4 aut |
700 | 1 | a Sulem, Patrick4 aut |
700 | 1 | a Tai, E Shyong4 aut |
700 | 1 | a Teo, Yik Ying4 aut |
700 | 1 | a Teslovich, Tanya4 aut |
700 | 1 | a Thorsteinsdottir, Unnur4 aut |
700 | 1 | a Trimmer, Jeff K4 aut |
700 | 1 | a Tuomi, Tiinamaija4 aut |
700 | 1 | a Tuomilehto, Jaakko4 aut |
700 | 1 | a Vaziri Sani, Faribau Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups4 aut0 (Swepub:lu)fa3255va |
700 | 1 | a Voight, Benjamin F4 aut |
700 | 1 | a Wilson, James G4 aut |
700 | 1 | a Boehnke, Michael4 aut |
700 | 1 | a McCarthy, Mark I4 aut |
700 | 1 | a Njølstad, Pål R4 aut |
700 | 1 | a Pedersen, Oluf4 aut |
700 | 1 | a Groop, Leifu Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups4 aut0 (Swepub:lu)endo-lgr |
700 | 1 | a Cox, David R4 aut |
700 | 1 | a Stefansson, Kari4 aut |
700 | 1 | a Altshuler, David4 aut |
710 | 2 | a Uppsala universitetb Kardiovaskulär epidemiologi4 org |
773 | 0 | t Nature Geneticsd : Springer Science and Business Media LLCg 46:4, s. 357-357q 46:4<357-357x 1546-1718x 1061-4036 |
856 | 4 | u http://www.ncbi.nlm.nih.gov/pubmed/24584071?dopt=Abstracty FULLTEXT |
856 | 4 | u http://dx.doi.org/10.1038/ng.2915y FULLTEXT |
856 | 4 | u https://europepmc.org/articles/pmc4051628?pdf=render |
856 | 4 8 | u https://lup.lub.lu.se/record/4384198 |
856 | 4 8 | u https://doi.org/10.1038/ng.2915 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-225085 |
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