Silver K, Walston J, Plotnick L, Taylor S I, Kahn C R, Shuldiner A R
Johns Hopkins University School of Medicine, Division of Endocrinology and Metabolism, Baltimore, Maryland 21287, USA.
J Clin Endocrinol Metab. 1997 Oct;82(10):3395-8. doi: 10.1210/jcem.82.10.4314.
Total congenital lipoatrophic diabetes is characterized by absence of subcutaneous adipose tissue, hypertriglyceridemia, and insulin resistance. We hypothesized that mutations in the beta-3-adrenergic receptor (beta 3AR) gene might result in the lipoatrophic phenotype by preventing triglyceride storage in adipocytes; thereby, resulting in secondary insulin resistance. We screened the beta 3AR 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 beta 3AR gene do not appear to be involved in the development of congenital total lipoatrophy.
先天性全身性脂肪萎缩性糖尿病的特征为缺乏皮下脂肪组织、高甘油三酯血症和胰岛素抵抗。我们推测β-3-肾上腺素能受体（β3AR）基因突变可能通过阻止甘油三酯在脂肪细胞中储存而导致脂肪萎缩表型，进而导致继发性胰岛素抵抗。我们对7例先天性全身性脂肪萎缩性糖尿病患者的β3AR基因进行了筛查。我们在3名非裔美国脂肪萎缩同胞和1名无脂肪萎缩但有胰岛素抵抗的同胞的3′非翻译区5′端发现了一个-153位鸟嘌呤到胞嘧啶的杂合性替代（G-153C）。为了确定这种碱基变化是否与脂肪萎缩表型有关，我们对69名无脂肪萎缩的非裔美国人进行了基因分型，发现2名对照受试者中有G-153C替代（等位基因频率=0.01）。在7名脂肪萎缩受试者中均未发现其他单链多态性变异。对1名脂肪萎缩受试者的两个等位基因进行直接测序，结果显示两个等位基因在-300位均有胸腺嘧啶插入缺失。所有脂肪萎缩受试者以及20名非裔美国对照受试者在该碱基插入缺失位点均为纯合子，提示已发表序列存在错误。总之，β3AR基因突变似乎与先天性全身性脂肪萎缩的发生无关。
