Type 2 diabetes sex-specific effects associated with E167K coding variant in TM6SF2
Summary: The rs58542926C >T (E167K) variant of the transmembrane 6 superfamily member 2 gene (TM6SF2) is associated with increased risks for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). Nevertheless, the role of the TM6SF2 rs58542926 variant in glucose metabolism is poorly...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Elsevier
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/123d0eb5291545f598be4e64a51063ec |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:123d0eb5291545f598be4e64a51063ec |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:123d0eb5291545f598be4e64a51063ec2021-11-20T05:08:18ZType 2 diabetes sex-specific effects associated with E167K coding variant in TM6SF22589-004210.1016/j.isci.2021.103196https://doaj.org/article/123d0eb5291545f598be4e64a51063ec2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221011640https://doaj.org/toc/2589-0042Summary: The rs58542926C >T (E167K) variant of the transmembrane 6 superfamily member 2 gene (TM6SF2) is associated with increased risks for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). Nevertheless, the role of the TM6SF2 rs58542926 variant in glucose metabolism is poorly understood. We performed a sex-stratified analysis of the association between the rs58542926C >T variant and T2D in multiple cohorts. The E167K variant was significantly associated with T2D, especially in males. Using an E167K knockin (KI) mouse model, we found that male but not the female KI mice exhibited impaired glucose tolerance. As an ER membrane protein, TM6SF2 was found to interact with inositol-requiring enzyme 1 α (IRE1α), a primary ER stress sensor. The male Tm6sf2 KI mice exhibited impaired IRE1α signaling in the liver. In conclusion, the E167K variant of TM6SF2 is associated with glucose intolerance primarily in males, both in humans and mice.Yanbo FanBrooke N. WolfordHaocheng LuWenying LiangJinjian SunWei ZhouOren RomAnubha MahajanIda SurakkaSarah E. GrahamZhipeng LiuHyunbae KimShweta RamdasLars G. FritscheJonas B. NielsenMaiken Elvestad GabrielsenKristian HveemDongshan YangJun SongMinerva T. Garcia-BarrioJifeng ZhangWanqing LiuKezhong ZhangCristen J. WillerY. Eugene ChenElsevierarticlePhysiologyMolecular physiologyDiabetologyGenomicsScienceQENiScience, Vol 24, Iss 11, Pp 103196- (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Physiology Molecular physiology Diabetology Genomics Science Q |
| spellingShingle |
Physiology Molecular physiology Diabetology Genomics Science Q Yanbo Fan Brooke N. Wolford Haocheng Lu Wenying Liang Jinjian Sun Wei Zhou Oren Rom Anubha Mahajan Ida Surakka Sarah E. Graham Zhipeng Liu Hyunbae Kim Shweta Ramdas Lars G. Fritsche Jonas B. Nielsen Maiken Elvestad Gabrielsen Kristian Hveem Dongshan Yang Jun Song Minerva T. Garcia-Barrio Jifeng Zhang Wanqing Liu Kezhong Zhang Cristen J. Willer Y. Eugene Chen Type 2 diabetes sex-specific effects associated with E167K coding variant in TM6SF2 |
| description |
Summary: The rs58542926C >T (E167K) variant of the transmembrane 6 superfamily member 2 gene (TM6SF2) is associated with increased risks for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). Nevertheless, the role of the TM6SF2 rs58542926 variant in glucose metabolism is poorly understood. We performed a sex-stratified analysis of the association between the rs58542926C >T variant and T2D in multiple cohorts. The E167K variant was significantly associated with T2D, especially in males. Using an E167K knockin (KI) mouse model, we found that male but not the female KI mice exhibited impaired glucose tolerance. As an ER membrane protein, TM6SF2 was found to interact with inositol-requiring enzyme 1 α (IRE1α), a primary ER stress sensor. The male Tm6sf2 KI mice exhibited impaired IRE1α signaling in the liver. In conclusion, the E167K variant of TM6SF2 is associated with glucose intolerance primarily in males, both in humans and mice. |
| format |
article |
| author |
Yanbo Fan Brooke N. Wolford Haocheng Lu Wenying Liang Jinjian Sun Wei Zhou Oren Rom Anubha Mahajan Ida Surakka Sarah E. Graham Zhipeng Liu Hyunbae Kim Shweta Ramdas Lars G. Fritsche Jonas B. Nielsen Maiken Elvestad Gabrielsen Kristian Hveem Dongshan Yang Jun Song Minerva T. Garcia-Barrio Jifeng Zhang Wanqing Liu Kezhong Zhang Cristen J. Willer Y. Eugene Chen |
| author_facet |
Yanbo Fan Brooke N. Wolford Haocheng Lu Wenying Liang Jinjian Sun Wei Zhou Oren Rom Anubha Mahajan Ida Surakka Sarah E. Graham Zhipeng Liu Hyunbae Kim Shweta Ramdas Lars G. Fritsche Jonas B. Nielsen Maiken Elvestad Gabrielsen Kristian Hveem Dongshan Yang Jun Song Minerva T. Garcia-Barrio Jifeng Zhang Wanqing Liu Kezhong Zhang Cristen J. Willer Y. Eugene Chen |
| author_sort |
Yanbo Fan |
| title |
Type 2 diabetes sex-specific effects associated with E167K coding variant in TM6SF2 |
| title_short |
Type 2 diabetes sex-specific effects associated with E167K coding variant in TM6SF2 |
| title_full |
Type 2 diabetes sex-specific effects associated with E167K coding variant in TM6SF2 |
| title_fullStr |
Type 2 diabetes sex-specific effects associated with E167K coding variant in TM6SF2 |
| title_full_unstemmed |
Type 2 diabetes sex-specific effects associated with E167K coding variant in TM6SF2 |
| title_sort |
type 2 diabetes sex-specific effects associated with e167k coding variant in tm6sf2 |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/123d0eb5291545f598be4e64a51063ec |
| work_keys_str_mv |
AT yanbofan type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT brookenwolford type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT haochenglu type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT wenyingliang type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT jinjiansun type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT weizhou type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT orenrom type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT anubhamahajan type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT idasurakka type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT sarahegraham type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT zhipengliu type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT hyunbaekim type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT shwetaramdas type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT larsgfritsche type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT jonasbnielsen type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT maikenelvestadgabrielsen type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT kristianhveem type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT dongshanyang type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT junsong type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT minervatgarciabarrio type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT jifengzhang type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT wanqingliu type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT kezhongzhang type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT cristenjwiller type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 AT yeugenechen type2diabetessexspecificeffectsassociatedwithe167kcodingvariantintm6sf2 |
| _version_ |
1718419525360156672 |