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Diabetes 51:1640-1643, 2002
© 2002 by the American Diabetes Association, Inc.

Brief Genetics Reports

Positional Candidate Gene Analysis of Lim Domain Homeobox Gene (Isl-1) on Chromosome 5q11-q13 in a French Morbidly Obese Population Suggests Indication for Association With Type 2 Diabetes

Mouna Barat-Houari1, Karine Clément2, Vincent Vatin1, Christian Dina1, Geneviève Bonhomme2, Francis Vasseur1, Bernard Guy-Grand2, and Philippe Froguel1,3

1 Institute of Biology, Centre National de la Recherche Scientifique (CNRS) 80-90, Lille, France
2 Laboratory and Department of Medicine and Nutrition-EA3502, Paris, France
3 Barts and the London Genome Center, Queen Mary’s School of Medicine, London, U.K.

The Lim domain homeobox gene (Isl-1) is a positional candidate gene for obesity that maps on chromosome 5q11-q13, a locus linked to BMI and leptin levels in French Caucasians. Isl-1 might be involved in body weight regulation and glucose homeostasis via the activation of proglucagon gene expression, which encodes for glucagon and glucagon-like peptides. By mutation screening of 72 obese subjects, we identified three single-nucleotide polymorphisms (SNPs) in the Isl1 gene. The allele frequencies in the morbidly obese group did not differ from that of the control group. In the obese group, the -47G allele was associated with a decreased risk of type 2 diabetes (odds ratio 0.41, P = 0.019). The AG bearers displayed a higher maximal BMI than the AA bearers in the whole obese group (P = 0.026) as well as in the type 2 diabetic obese subgroup (P = 0.014). In obese families, this allele was not preferentially transmitted from heterozygous parents to their obese siblings, indicating that Isl-1 does not contribute to the linkage with obesity on 5cen-q. However, in French Caucasian morbidly obese subjects, the Isl1-47A->G SNP may modulate the risk for type 2 diabetes and may increase body weight in diabetic morbidly obese subjects.


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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2002 by the American Diabetes Association.