Work

Uncoupling Protein 2 Region on Chromosome 11q13 Is not Linked to Markers of Obesity in Familial Type 2 Diabetes

Year: 1997

Type: article

Abstract: O besity is an important factor in the predisposition to type 2 diabetes and shows familial tendencies similar to diabetes.We studied 42 families selected for having a type 2 diabetic sibling pair with diabetes onset before age 65 years and with grandparents of Northern European extraction.Although obesity was not included in the ascertainment criteria, we demonstrated Mendelian inheritance of obesity as measured by BMI in these families with evidence for two segregating recessive loci: a locus for moderate obesity and one for extreme obesity (mean BMI 32 and 39 kg/m 2 , respectively).Nonetheless, examination of nine candidate genes for obesity, including the leptin and leptin receptor genes (markers in the region homologous to agouti, lipoprotein lipase, and tumor necrosis factor-a [TNF-a]), showed no evidence for linkage to BMI in these families (1).Although a common mutation in the (3-3 adrenergic receptor gene is reported to cause earlier onset type 2 diabetes, insulin resistance, and more extreme obesity in some studies (2-4), we were unable to demonstrate any effect of this variant within families with multiple type 2 diabetic siblings.The inherited propensity to obesity might result from genetic factors that control energy expenditure, hi rodents, mitochondrial uncoupling protein-1 (UCP1) has been implicated in energy expenditure in brown adipose tissue (5), but brown adipose does not appear to be an important source of energy expenditure in humans.However, two groups (6,7) recently cloned a protein with 59% amino acid homology to UCP, which is expressed in both muscle and white adipose tissue.Like UCP1, UCP2 or UCP homolog appears to cause a mitochondrial proton leak and may be involved in energy balance and weight regulation (6).This gene has been mapped to mouse chromosome 7 near several proposed mouse quantitative trait loci for obesity (6).The UCP2 locus was placed From the Division of Endocrinology (S.

Source: Diabetes

DOI: 10.2337/diab.46.12.2105

Authors: Steven C Elbein, Mark Leppert, Sandra Hasstedt

Institutions: University of Arkansas for Medical Sciences, University of Utah

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze