Genetic Variation in the Small Heterodimer Partner Gene and Young-Onset Type 2 Diabetes, Obesity, and Birth Weight in U.K. Subjects
Genetic Variation in the Small Heterodimer Partner Gene and Young-Onset Type 2 Diabetes, Obesity, and Birth Weight in U.K. Subjects Simon M.S. Mitchell 1 , Michael N. Weedon 1 , Katharine R. Owen 1 , Beverley Shields 1 , Beverley Wilkins-Wall 1 , Mark Walker 2 , Mark I. McCarthy 3 , Timothy M. Frayl...
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Published in | Diabetes (New York, N.Y.) Vol. 52; no. 5; pp. 1276 - 1279 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.05.2003
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Subjects | |
Online Access | Get full text |
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Summary: | Genetic Variation in the Small Heterodimer Partner Gene and Young-Onset Type 2 Diabetes, Obesity, and Birth Weight in U.K.
Subjects
Simon M.S. Mitchell 1 ,
Michael N. Weedon 1 ,
Katharine R. Owen 1 ,
Beverley Shields 1 ,
Beverley Wilkins-Wall 1 ,
Mark Walker 2 ,
Mark I. McCarthy 3 ,
Timothy M. Frayling 1 and
Andrew T. Hattersley 1
1 Centre for Molecular Genetics, Peninsula Medical School, Exeter, U.K
2 Department of Medicine, School of Medicine, Newcastle upon-Tyne, U.K
3 Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Infirmary, Oxford, U.K
Abstract
The orphan receptor small heterodimer partner (SHP, NR0B2) modulates the transcription activity of the MODY1 gene HNF4a . Mutations in SHP were found in 7% of Japanese obese young-onset type 2 diabetic patients and were associated with moderate obesity and increased
birth weight. We investigated SHP in 1927 U.K. subjects, examining relationships with type 2 diabetes, obesity, and birth weight. Sequencing of the coding
region of SHP in 122 obese, young-onset type 2 diabetic patients detected the polymorphism G171A. The polymorphism was not associated with
diabetes in case control or familial association studies. The A allele (frequency 0.07) was not associated with obesity in
type 2 diabetic subjects ( n = 348), their parents ( n = 272), or young nondiabetic adults ( n = 925). However, the rare (<1%) AA homozygotes had a raised BMI in each cohort; this was significant when all cohorts were
combined ( Z score = 0.67 AA vs. −0.05 G/x, P = 0.02). There was no association with corrected birth weight in 382 normal babies, but the only AA baby was 4,069 g. Our
study suggests that genetic variation in SHP is unlikely to be common in the predisposition to diabetes, obesity, or increased birth weight in U.K. Caucasians.
Footnotes
Address correspondence and reprint requests to Dr. Timothy M. Frayling, Diabetes and Vascular Medicine, Peninsula Medical
School, Barrack Road, Exeter EX2 5AX, U.K. E-mail: t.m.frayling{at}exeter.ac.uk .
Received for publication 9 August 2002 and accepted in revised form 20 December 2002.
HNF, hepatocyte nuclear factor; LOD, logarithm of odds; MODY, maturity-onset diabetes of the young; SHP, small heterodimer
partner; TDT, transmission disequilibrium test.
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/diabetes.52.5.1276 |