Total congenital lipoatrophic diabetes is characterized by absence of subcutaneous adipose tissue, hypertriglyceridemia, and insulin resistance. We hypothesized that mutations in the β-3-adrenergic receptor (β3AR) gene might result in the lipoatrophic phenotype by preventing triglyceride storage in adipocytes; thereby, resulting in secondary insulin resistance. We screened the β3AR gene in 7 subjects with total congenital lipoatropic diabetes. We found a heterozygous substitution of a guanine to cytosine at position - 153 (G-153C) in the 5'-untranslated region of 3 African-American lipoatrophic siblings and 1 sibling without lipoatrophy but with insulin resistance. To determine whether the base change was related to the lipoatrophic phenotype, we genotyped 69 African-Americans without lipoatrophy and found the G-153C substitution in 2 control subjects (allele frequency = 0.01). No other single-stranded polymorphism variants were found in any of the 7 lipoatrophic subjects. Direct sequencing of both alleles of 1 lipoatrophic subject demonstrated a thymidine insertion at position - 300 in both alleles. All lipoatrophic subjects along with 20 African-American control subjects were homozygous for the base insertion, suggesting an error in the published sequence. In conclusion, mutations in the β3AR gene do not appear to be involved in the development of congenital total lipoatrophy.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical