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Common variants in ...
Common variants in HNF-1 alpha and risk of type 2 diabetes.
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- Holmkvist, Johan (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Skånes universitetssjukhus (SUS),Skåne University Hospital
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- Cervin, C (författare)
- Skånes universitetssjukhus (SUS),Skåne University Hospital,Karolinska universitetssjukhuset,Karolinska University Hospital
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- Lyssenko, Valeriya (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Skånes universitetssjukhus (SUS),Skåne University Hospital
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- Winckler, W (författare)
- Broad Institute,Massachusetts General Hospital
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- Anevski, Dragi (författare)
- Gothenburg University,Lund University,Lunds universitet,Matematisk statistik,Matematikcentrum,Institutioner vid LTH,Lunds Tekniska Högskola,Mathematical Statistics,Centre for Mathematical Sciences,Departments at LTH,Faculty of Engineering, LTH,Göteborgs universitet,University of Gothenburg,Chalmers tekniska högskola,Chalmers University of Technology,Institutionen för matematiska vetenskaper,Department of Mathematical Sciences
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- Cilio, Corrado (författare)
- Lund University,Lunds universitet,Diabetes - immunovirologi,Forskargrupper vid Lunds universitet,Diabetes - Immunovirology,Lund University Research Groups
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- Almgren, Peter (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Skånes universitetssjukhus (SUS),Skåne University Hospital
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- Berglund, Göran (författare)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skånes universitetssjukhus (SUS),Skåne University Hospital
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- Nilsson, P (författare)
- Skånes universitetssjukhus (SUS),Skåne University Hospital
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- Tuomi, Tiinamaija (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Folkhalsan,Helsinki University Central Hospital
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Lindgren, C (författare)
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- Altshuler, D (författare)
- Broad Institute,Massachusetts General Hospital
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- Groop, Leif (författare)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Helsinki University Central Hospital,Skånes universitetssjukhus (SUS),Skåne University Hospital
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(creator_code:org_t)
- 2006-10-11
- 2006
- Engelska.
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 49:Oct 11, s. 2882-2891
- Relaterad länk:
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Abstract
Ämnesord
Stäng
- Mutations in the hepatocyte nuclear factor 1-alpha gene (HNF-1 alpha, now known as the transcription factor 1 gene [TCF1]) cause the most common monogenic form of diabetes, MODY3, but it is not known if common variants in HNF-1a are associated with decreased transcriptional activity or phenotypes related to type 2 diabetes, or whether they predict future type 2 diabetes. We studied the effect of four common polymorphisms (rs1920792, I27L, A98V and S487N) in and upstream of the HNF-1 alpha gene on transcriptional activity in vitro, and their possible association with type 2 diabetes and insulin secretion in vivo. Certain combinations of the I27L and A98V polymorphisms in the HNF-1 alpha gene showed decreased transcriptional activity on the target promoters glucose transporter 2 (now known as solute carrier family 2 [facilitated glucose transporter], member 2) and albumin in both HeLa and INS-1 cells. In vivo, these polymorphisms were associated with a modest but significant impairment in insulin secretion in response to oral glucose. Insulin secretion deteriorated over time in individuals carrying the V allele of the A98V polymorphism (n=2,293; p=0.003). In a new case-control (=1,511 and n=2,225 respectively) data set, the I27L polymorphism was associated with increased risk of type 2 diabetes, odds ratio (OR)=1.5 (p=0.002; multiple logistic regression), particularly in elderly (age > 60 years) and overweight (BMI > 25 kg/m(2)) patients (OR=2.3, p=0.002). This study provides in vitro and in vivo evidence that common variants in the MODY3 gene, HNF-1 alpha, influence transcriptional activity and insulin secretion in vivo. These variants are associated with a modestly increased risk of late-onset type 2 diabetes in subsets of elderly overweight individuals.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
Nyckelord
- insulin
- MODY3
- prospective studies
- type 2 diabetes
- mellitus
- factor 1-alpha
- case-control studies
- association study
- glucose
- hepatocyte nuclear
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Holmkvist, Johan
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Cervin, C
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Lyssenko, Valeri ...
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Winckler, W
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Anevski, Dragi
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Cilio, Corrado
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visa fler...
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Almgren, Peter
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Berglund, Göran
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Nilsson, P
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Tuomi, Tiinamaij ...
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Lindgren, C
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Altshuler, D
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Groop, Leif
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Dermatologi och ...
- Artiklar i publikationen
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Diabetologia
- Av lärosätet
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Lunds universitet
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Chalmers tekniska högskola
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Göteborgs universitet
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Karolinska Institutet