P-118: Insulin sensitivity and body weight changes in young Caurcasian carriers of the codon 64 amino acid polymorphism of the β3-adrenergic receptor gene

Background: Polycystic ovary syndrome (PCOS) is a multifactorial and heterogeneous disease that has a potent inheritable component based on familial clustering. Despite many studies in the genetic field of PCOS, the genes that are involved in the causes of this syndrome have not been thoroughly investigated. Objective: The purpose of this study was to establish the occurrence of the Trp64Arg polymorphism of beta3 adrenergic receptor in non-obese women with PCOS. Materials and Methods: This cross-sectional study was performed on 100 women with PCOS and normal women as the control group in Imam Khomeini Hospital of Tehran in 2016-2017. Peripheral blood sample (2 cc) was obtained from two groups for genomic DNA based on the gene bank. Polymorphisms were genotyped by of using ADRB3 Trp64Arg. Then the DNA was extracted by genomic kiagen kit. The primer was analyzed for PCR based on gene bank by using Primer3 software and then confirmed by primer Blast tool at NCBI site to conformity to the beta-3 adrenergic receptor gene. The protein changes were assessment by the Clastal W software. Results: The sequence analysis presented in NCBI, transcript variant 1, with the code NM_000025.2, shows changes in the amino acid sequence of exon 1 in women with PCOS. Polymorphism in the codon 64 encoding the amino acid tryptophan (W) occurred in the nucleotide c.T190C, which changed the nucleotide T to C and then the amino acid sequence of the tryptophan was altered to arginine pW64R. Conclusion: T-C polymorphism is evident in the codon 64 of the adrenergic β3 receptor in patients with PCOS. Therefore, Beta3 adrenergic receptor gene polymorphism (Thr164Ile) associates with this syndrome in nonobese women. Key words: Codon 64, Beta-3 adrenergic receptor, Polymorphism, Polycystic ovarian syndrome.

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Lack of Association between the Trp64Arg Mutation in the β3-Adrenergic Receptor Gene and Obesity in Japanese Men: A Longitudinal Analysis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.4.3872 ◽

1997 ◽

Vol 82 (4) ◽

pp. 1284-1287 ◽

Cited By ~ 1

Author(s):

Terumasa Nagase ◽

Akira Aoki ◽

Michiko Yamamoto ◽

Hiroko Yasuda ◽

Seijiro Kado ◽

...

Keyword(s):

Body Weight ◽

Adrenergic Receptor ◽

Receptor Gene ◽

Adult Life ◽

Dependent Diabetes Mellitus ◽

Heterozygous Mutation ◽

Homozygous Mutation ◽

Japanese Men ◽

The Difference ◽

Adrenergic Receptor Gene

Abstract The β3-adrenergic receptor (β3AR) is implicated in the regulation of thermogenesis and lipolysis, and it is suggested that the Trp64Arg mutation in this receptor may contribute to the development of obesity. To examine whether the Trp64Arg mutation had any effect on body weight during adult life, the β3AR genotype was determined in 186 unselected Japanese men, most of whom had records of body weight measured yearly from 25–53 yr of age. Of them, 26 subjects were diagnosed as having noninsulin-dependent diabetes mellitus (NIDDM) and 41 as having impaired glucose tolerance. There were 6 subjects (3%) with homozygous mutation, 67 (36%) with heterozygous mutation, and 113 (61%) with normal allele. Among the 3 genotypes, there were no significant differences in body mass index (BMI) at any age between 25–53 yr and the prevalence of NIDDM at the age of 53 yr. When longitudinal changes in body weight were compared between subjects with and without mutation, the former were less prone to gain weight than the latter. The frequency of the mutant allele was 1) not different among obese (BMI, >26.4), intermediate (BMI, 22–26.4), and nonobese (BMI, <22.0) subjects (0.21, 0.22, and 0.26, respectively; P = 0.77); 2) lower in subjects with NIDDM than in those without it, but the difference was insignificant (0.12 vs. 0.23; P = 0.07); and 3) similar between 186 unselected men and another group of 100 patients with NIDDM that were randomly selected for comparison (0.21 vs. 0.23). These results suggest that the β3AR is not a major contributing factor to obesity or NIDDM in Japanese men.

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

Acta Endocrinologica ◽

10.1530/eje.0.1440291 ◽

2001 ◽

pp. 291-295 ◽

Cited By ~ 9

Author(s):

A Hamann ◽

C Brieske ◽

J Tafel ◽

P Buttron ◽

B Schwarzloh ◽

...

Keyword(s):

Body Weight ◽

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Lipolytic Activity ◽

Receptor Gene ◽

Single Strand Conformation Polymorphism ◽

Normal Weight ◽

Coding Region ◽

Gene Encoding ◽

Adrenergic Receptor Gene

OBJECTIVE: The alpha(2)-adrenergic receptors are involved in the effects of catecholamines on energy metabolism. Of three known subtypes with differential expression, alpha(2A)-adrenergic receptors are also localized in adipose tissue where they counteract the lipolytic activity of beta-adrenergic receptors. This study was undertaken to assess whether variants in the alpha(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 alpha(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 alpha(2A)-adrenergic receptor gene are unlikely to contribute to the predisposition for the lean or obese state.

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