Identification of a deletion variant in the gene encoding the human alpha(2A)-adrenergic receptor

Abstract

Objective: The a 2 -adrenergic receptors are involved in the effects of catecholamines on energy metabolism. Of three known subtypes with differential expression, a 2A -adrenergic receptors are also localized in adipose tissue where they counteract the lipolytic activity of b-adrenergic receptors. This study was undertaken to assess whether variants in the a 2A -adrenergic receptor gene are associated with body weight. Design and methods: Single strand conformation polymorphism (SSCP) screening and subsequent sequencing were applied to determine genetic variants in DNA samples from individuals with obesity, those of normal weight and those underweight. Results: Analysis of the coding region resulted in the identification of an 18 bp deletion, with no other mutation found. Of 429 genotyped subjects, 7 carried the deletion, with no significant differences between lean and obese subjects. A previously identified polymorphism in the promoter of the a 2A -adrenergic receptor gene also did not show an association with any of the tested body weight categories. Conclusion: Our data suggest that variants in the a 2A -adrenergic receptor gene are unlikely to contribute to the predisposition for the lean or obese state.

Pharmacology and Physiology of Human Adrenergic Receptor polymorphisms

“…For most of the noncoding polymorphisms, no associations have been found with multiple pathological conditions linked to α 2A AR function, including hypertension, panic and mood disorders, schizophrenia, and obesity (92,99,(101)(102)(103)(104)(105). In contrast, several clinical phenotypes, including hypertension, body fat distribution, and glucose metabolism, have been shown to be associated with a Dra I restriction fragment length polymorphism within the 3 UTR (106)(107)(108)(109).…”

The Human Obesity Gene Map: The 2001 Update

“…Among these studies, the most frequent ones were those pertaining to markers of ADRB3 (eight studies) (63, 82, 86, 87, 88, 89, 90, 91), TNF (six studies) (50, 92, 93, 94, 95, 96), UCP3 (five studies) (58, 63, 70, 97, 98), and PPARG (four studies) (63, 99, 100, 101). Other markers yielding negative findings were those related to angiotensin converting enzyme (ACE) (102), alpha‐2A adrenergic receptor (ADRA2A) (103), ADRA2B (83), ADRB2 (104, 105), agouti‐related protein (AGRP) (11, 106), apolipoprotein B (APOB) (107), APOE (63), cholecystokinin (CCK) (108), corticotropin‐releasing hormone (CRH) (109), fatty acid binding protein 2 (FABP2) (110), guanine nucleotide binding protein (G‐protein) beta polypeptide 3 (GNB3) (111, 112), GRL (113, 114), LEPR (63, 115), lamin A/C (LMNA) (116), lipoprotein lipase (LPL) (117), lymphotoxin‐alpha (LTA) (118), methylenetetrahydrofolate reductase (MTHFR) (119), (NDN) (120), POMC (121), PPARA (62), uncoupling protein 1 (UCP1) (90, 122), and uncoupling protein 2 (UCP2) (63).…”

Alpha-2-adrenergic receptor gene polymorphism in Turkish population with irritable bowel syndrome

“…However, it should be remembered that the allele frequencies and genetic distributions of these polymorphisms differ in different geographic areas. Several studies have shown that the frequency of 1291G allele is high in Japanese (31), Taiwan (32), Swedish (33), and Chinese (34) population (72, 70, 77, and 70%, respectively), whereas it is only 1% in Germans (35). This broad spectrum of allele frequencies shows the importance of ethnic control over the genetic differences.…”