Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in dutch Caucasians

Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians. Objectives: To investigate the broader significance of this association for DM2, replication studies in distinct ethic populations are required. We investigated ATF6 for its association with DM2 in Dutch Caucasians. Design/Setting: A genetic association study was conducted at an academic research laboratory. Study Participants: Two independent Dutch coh... Mehr ...

Verfasser: Meex, Steven J. R.
van Greevenbroek, Marleen M. J.
Ayoubi, Torik A.
Vlietinck, Robert
van Vliet-Ostaptchouk, Jana V.
Hofker, Martin H.
Vermeulen, Vicky M. M. -J.
Schalkwijk, Casper G.
Feskens, Edith J. M.
Boer, Jolanda M. A.
Stehouwer, Coen D. A.
van der Kallen, Carla J. H.
de Bruin, Tjerk W. A.
Dokumenttyp: Artikel
Erscheinungsdatum: 2007
Reihe/Periodikum: Meex , S J R , van Greevenbroek , M M J , Ayoubi , T A , Vlietinck , R , van Vliet-Ostaptchouk , J V , Hofker , M H , Vermeulen , V M M -J , Schalkwijk , C G , Feskens , E J M , Boer , J M A , Stehouwer , C D A , van der Kallen , C J H & de Bruin , T W A 2007 , ' Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in dutch Caucasians ' , Journal of Clinical Endocrinology and Metabolism , vol. 92 , no. 7 , pp. 2720-2725 . https://doi.org/10.1210/jc.2006-2280
Schlagwörter: ENDOPLASMIC-RETICULUM STRESS / ER STRESS / MESSENGER-RNA / INTOLERANCE / POPULATION / VARIANTS / MELLITUS / OBESITY / ATF6
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29028088
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://hdl.handle.net/11370/775fc271-12f5-4c1f-8059-2415538fadcd

Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians. Objectives: To investigate the broader significance of this association for DM2, replication studies in distinct ethic populations are required. We investigated ATF6 for its association with DM2 in Dutch Caucasians. Design/Setting: A genetic association study was conducted at an academic research laboratory. Study Participants: Two independent Dutch cohorts were studied. Cohort 1 (n = 154) was used to evaluate genetic variation in the ATF6 gene in relation to glucose homeostasis in the general population. Cohort 2 (n = 798) consisted of patients with DM2, impaired glucose tolerance, impaired fasting glucose, and normoglycemic control subjects, and was used to investigate ATF6 polymorphisms for their contribution to disturbed glucose homeostasis and DM2. Main Outcome Measures: There were 16 tag single nucleotide polymorphisms genotyped in all subjects of both cohorts. Those single nucleotide polymorphisms included three nonsynonymous coding variants and captured all common allelic variation of ATF6. Results: Our data show that common ATF6 variants are associated with elevated glucose levels in the general population (cohort 1, P = 0.005-0.05). Furthermore, the majority of these variants, and haplotypes thereof, were significantly associated with impaired fasting glucose, impaired glucose tolerance, and DM2 ( cohort 2, P = 0.006-0.05). Associated variants differ from those identified in Pima Indians. Conclusions: Our results strengthen the evidence that one or more variants in ATF6 are associated with disturbed glucose homeostasis and DM2.