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.
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.
Barat-Houari
Mouna
M
Institute of Biology, Centre National de la Recherche Scientifique (CNRS) 80-90, Lille, France.
Clément
Karine
K
Vatin
Vincent
V
Dina
Christian
C
Bonhomme
Geneviève
G
Vasseur
Francis
F
Guy-Grand
Bernard
B
Froguel
Philippe
P
D000328:Adult; D000368:Aged; D002895:Chromosomes, Human, Pair 5; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009765:Obesity; D009767:Obesity, Morbid / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1