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Apolipoprotein E genotype, islet amyloid deposition and severity of type 2 diabetes

Apolipoprotein E genotype, islet amyloid deposition and severity of type 2 diabetes
Apolipoprotein E genotype, islet amyloid deposition and severity of type 2 diabetes

Islet amyloid is found in 90% of patients with Type 2 (non-insulin-dependent) diabetes at post-mortem. More extensive amyloidosis is associated with decreased islet function and requirement for insulin therapy. Severity of cerebral amyloidosis in Alzheimer's disease (AD) is increased in subjects with the apolipoprotein E (ApoE) ε4 allele. To determine if ApoE genotype was associated with severity of islet amyloidosis and diabetes, samples were genotyped from 32 specimens of post-mortem pancreas and from patients classified by disease progression. DNA was extracted from blood samples from Caucasian patients diagnosed with Type 2 diabetes, at age >40 years, classified according to disease progression: group 1 on oral therapy for at least 10 years from diagnosis, (n=147) and group 2, requiring insulin within 6 years from diagnosis, (n=187). ApoE genotype was determined by restriction-fragment length polymorphism analysis. DNA in pancreatic extracts (23 diabetic; 9 non-diabetic subjects) showed no association of ApoE polymorphisms with either degree of islet amyloidosis or disease severity. The distributions of ApoE ε2, ε3 and ε4 were similar in both clinical patient groups and in the non-diabetic group and unrelated to progression of disease. It is unlikely that the common polymorphisms for the ApoE gene are linked to amyloid formation or progression of islet dysfunction in Type 2 diabetes.

Amyloid, Apolipoprotein E, Diabetes, Genetics, Islet
0168-8227
105-110
Powell, D.S.
40be6871-fccb-4207-a40d-925e26856e11
Maksoud, H.
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Chargé, S.B.P.
c7aac432-8095-47ae-8c81-e740e7bcbfe7
Moffitt, J.H.
72eed897-da8a-4264-914a-b93c7ec56d91
Desai, M.
ce71a871-9255-42ef-85b8-4b91e6119ebe
Da Silva Fihlo, R.L.
597de7c5-cf85-44ed-a387-2c288fa73b04
Hattersley, A.T.
27a38224-13bf-4e48-98d2-8e31e017a986
Stratton, I.M.
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Matthews, D.R.
ba1a878d-6510-45c5-896c-d4ade423caca
Levy, J.C.
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Clark, A.
e09cf35f-e678-452c-b179-4529fd011927
Powell, D.S.
40be6871-fccb-4207-a40d-925e26856e11
Maksoud, H.
938f0470-7989-4640-a87c-4a592d637c23
Chargé, S.B.P.
c7aac432-8095-47ae-8c81-e740e7bcbfe7
Moffitt, J.H.
72eed897-da8a-4264-914a-b93c7ec56d91
Desai, M.
ce71a871-9255-42ef-85b8-4b91e6119ebe
Da Silva Fihlo, R.L.
597de7c5-cf85-44ed-a387-2c288fa73b04
Hattersley, A.T.
27a38224-13bf-4e48-98d2-8e31e017a986
Stratton, I.M.
772f25b9-23c0-4240-a3f6-1e76b03b172f
Matthews, D.R.
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Levy, J.C.
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Clark, A.
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Powell, D.S., Maksoud, H., Chargé, S.B.P., Moffitt, J.H., Desai, M., Da Silva Fihlo, R.L., Hattersley, A.T., Stratton, I.M., Matthews, D.R., Levy, J.C. and Clark, A. (2003) Apolipoprotein E genotype, islet amyloid deposition and severity of type 2 diabetes. Diabetes Research and Clinical Practice, 60 (2), 105-110. (doi:10.1016/S0168-8227(02)00281-4).

Record type: Article

Abstract

Islet amyloid is found in 90% of patients with Type 2 (non-insulin-dependent) diabetes at post-mortem. More extensive amyloidosis is associated with decreased islet function and requirement for insulin therapy. Severity of cerebral amyloidosis in Alzheimer's disease (AD) is increased in subjects with the apolipoprotein E (ApoE) ε4 allele. To determine if ApoE genotype was associated with severity of islet amyloidosis and diabetes, samples were genotyped from 32 specimens of post-mortem pancreas and from patients classified by disease progression. DNA was extracted from blood samples from Caucasian patients diagnosed with Type 2 diabetes, at age >40 years, classified according to disease progression: group 1 on oral therapy for at least 10 years from diagnosis, (n=147) and group 2, requiring insulin within 6 years from diagnosis, (n=187). ApoE genotype was determined by restriction-fragment length polymorphism analysis. DNA in pancreatic extracts (23 diabetic; 9 non-diabetic subjects) showed no association of ApoE polymorphisms with either degree of islet amyloidosis or disease severity. The distributions of ApoE ε2, ε3 and ε4 were similar in both clinical patient groups and in the non-diabetic group and unrelated to progression of disease. It is unlikely that the common polymorphisms for the ApoE gene are linked to amyloid formation or progression of islet dysfunction in Type 2 diabetes.

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More information

Accepted/In Press date: 12 December 2002
e-pub ahead of print date: 11 April 2003
Published date: 1 May 2003
Additional Information: Funding Information: We are grateful to the Wellcome Trust (DP, SC, JHM, AC), the Medical Research Council UK (IMS), the Oxford Health Services Committee (AC, DRM, JCL) and Diabetes UK (MD, AH) for financial support and to the patients in Oxford and Exeter for their co-operation in this project.
Keywords: Amyloid, Apolipoprotein E, Diabetes, Genetics, Islet

Identifiers

Local EPrints ID: 487005
URI: http://eprints.soton.ac.uk/id/eprint/487005
ISSN: 0168-8227
PURE UUID: d0cd088e-1871-4271-b0bc-c25368cf2c04
ORCID for I.M. Stratton: ORCID iD orcid.org/0000-0003-1172-7865

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Date deposited: 09 Feb 2024 17:39
Last modified: 18 Mar 2024 04:01

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Contributors

Author: D.S. Powell
Author: H. Maksoud
Author: S.B.P. Chargé
Author: J.H. Moffitt
Author: M. Desai
Author: R.L. Da Silva Fihlo
Author: A.T. Hattersley
Author: I.M. Stratton ORCID iD
Author: D.R. Matthews
Author: J.C. Levy
Author: A. Clark

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