The sulfonylurea receptor (SUR) is a key component in glucose-stimulated insulin secretion. Obesity and NIDDM are frequently associated and share some metabolic abnormalities, suggesting that they might also share some susceptibility genes. Thus, the SUR encoding gene is a plausible candidate for a primary pancreatic β-cell defect and thus for hyperglycemia and weight gain. Through association and linkage studies, we have investigated the potential role of the SUR gene in families with NIDDM and in two independent sets of morbidly obese families. The exon 22 T-allele at codon 761 was more common in patients with NIDDM (7.7%) and morbid obesity (7.8%) than in control subjects (1.8%, P = 0.030 and P = 0.023, respectively). This variant was associated with morbid obesity (odds ratio 3.71, P = 0.017) and NIDDM (odds ratio 2.20, P = 0.04; association dependent on BMI). Although the frequencies for intron 24 variant were similar in all groups, morbidly obese patients homozygous for the c-allele had a more deleterious form of obesity. Sib-pair linkage studies with NIDDM in French Caucasian families gave no evidence for linkage to the SUR locus. However, in one set of the obese families, we found an indication for linkage with a SUR-linked microsatellite marker (D11S419, P = 0.0032). We conclude that in Caucasians, the SUR locus may contribute to the genetic susceptibility to NIDDM and obesity.
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Original Articles|
April 01 1997
Genetic Studies of the Sulfonylurea Receptor Gene Locus in NIDDM and in Morbid Obesity Among French Caucasians
El Habib Hani;
El Habib Hani
CNRS EP 10, Institut Pasteur and C.H.R.U.
Lille
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Karine Clément;
Karine Clément
CNRS EP 10, Institut Pasteur and C.H.R.U.
Lille
Départment de Nutrition, Hôtel-Dieu
Paris, France
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Gilberto Velho;
Gilberto Velho
INSERM U-358, Hôpital Saint-Louis
Paris, France
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Nathalie Vionnet;
Nathalie Vionnet
CNRS EP 10, Institut Pasteur and C.H.R.U.
Lille
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Jörg Hager;
Jörg Hager
CNRS EP 10, Institut Pasteur and C.H.R.U.
Lille
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Anne Philippi;
Anne Philippi
INSERM U-358, Hôpital Saint-Louis
Paris, France
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Christian Dina;
Christian Dina
CNRS EP 10, Institut Pasteur and C.H.R.U.
Lille
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Hiroshi Inoue;
Hiroshi Inoue
Division of Metabolism, Diabetes and Endocrinology, Department of Internal Medicine, Washington University School of Medicine
Saint Louis, Missouri
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M Alan Permutt;
M Alan Permutt
Division of Metabolism, Diabetes and Endocrinology, Department of Internal Medicine, Washington University School of Medicine
Saint Louis, Missouri
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Arnaud Basdevant;
Arnaud Basdevant
Départment de Nutrition, Hôtel-Dieu
Paris, France
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Michael North;
Michael North
Sequana Therapeutics Inc.
La Jolla, California
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Florence Demenais;
Florence Demenais
INSERM U-358, Hôpital Saint-Louis
Paris, France
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Bernard Guy-Grand;
Bernard Guy-Grand
Départment de Nutrition, Hôtel-Dieu
Paris, France
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Philippe Froguel
Philippe Froguel
CNRS EP 10, Institut Pasteur and C.H.R.U.
Lille
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Address correspondence and reprint requests to Dr. Philippe Froguel, CNRS EP-10, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP-245, 59019 Lille cedex, France.
1
E.H.H. and K.C. contributed equally to this work.
2
BIR, β-cell inwardly rectifying potassium channel; IBD, identical by descent; IKATP, pancreatic β-cell ATP-sensitive potassium channel; PCR, polymerase chain reaction; SUR, sulfonylurea receptor; TDT, transmission/disequilibrium test.
Diabetes 1997;46(4):688–694
Article history
Received:
April 25 1996
Revision Received:
November 14 1996
Accepted:
November 14 1996
PubMed:
9075812
Citation
El Habib Hani, Karine Clément, Gilberto Velho, Nathalie Vionnet, Jörg Hager, Anne Philippi, Christian Dina, Hiroshi Inoue, M Alan Permutt, Arnaud Basdevant, Michael North, Florence Demenais, Bernard Guy-Grand, Philippe Froguel; Genetic Studies of the Sulfonylurea Receptor Gene Locus in NIDDM and in Morbid Obesity Among French Caucasians. Diabetes 1 April 1997; 46 (4): 688–694. https://doi.org/10.2337/diab.46.4.688
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