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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.

Abstract
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.
AuthorsMouna Barat-Houari, Karine Clément, Vincent Vatin, Christian Dina, Geneviève Bonhomme, Francis Vasseur, Bernard Guy-Grand, Philippe Froguel
JournalDiabetes (Diabetes) Vol. 51 Issue 5 Pg. 1640-3 (May 2002) ISSN: 0012-1797 [Print] United States
PMID11978668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Nerve Tissue Proteins
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1
Topics
  • Adult
  • Aged
  • Chromosomes, Human, Pair 5
  • Diabetes Mellitus (epidemiology, genetics)
  • Diabetes Mellitus, Type 2 (epidemiology, genetics)
  • Female
  • France (epidemiology)
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genotype
  • Homeodomain Proteins (genetics)
  • Humans
  • LIM-Homeodomain Proteins
  • Male
  • Middle Aged
  • Nerve Tissue Proteins
  • Obesity
  • Obesity, Morbid (epidemiology, genetics)
  • Risk Factors
  • Transcription Factors

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