Analysis of 6 Single-Nucleotide Polymorphisms in the Androgen Receptor Gene in Chilean Patients With Primary Spermatogenic Failure

Background: Preclinical work revealed significant interactions between ligands of the histamine H3 receptor and different drugs of abuse. In the case of psychostimulants, the results reported are somewhat controversial and human data are still scarce, despite the fact that an inverse agonist of the H3 receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. Aims: We have studied associations between histamine H3 receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H3 receptor in drug abuse. Methods: Seven single nucleotide polymorphisms of the histamine H3 receptor gene were genotyped by using a multiplexing assay in 248 samples of subjects with cocaine use disorder and 500 randomized samples of subjects representative of the Spanish population. Results: The study of the epidemiological information associated to the samples revealed that subjects with cocaine use disorder broadly abused alcohol, tobacco and cannabinoids. Two single nucleotide polymorphisms (rs3787430 and rs74627870) were found significantly associated with the occurrence of addiction and one more (rs13042865) was specifically related to the severity of cocaine dependence within drug abusers. Conclusions: The associations found in this study further extend the hypothesis that histamine H3 receptor function could be relevant in drug abuse in general and cocaine addiction in particular.

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Single nucleotide substitution of the androgen receptor gene in a case with receptor-positive androgen insensitivity syndrome (complete form)

Acta Endocrinologica ◽

10.1530/acta.0.1280355 ◽

1993 ◽

Vol 128 (4) ◽

pp. 355-360 ◽

Cited By ~ 13

Author(s):

Hiroyuki Kasumi ◽

Shinji Komori ◽

Noriyuki Yamasaki ◽

Hiroki Shima ◽

Shinzo Isojima

Keyword(s):

Androgen Receptor ◽

Genetic Disorders ◽

Genetic Disorder ◽

Receptor Gene ◽

Androgen Receptor Gene ◽

Androgen Insensitivity Syndrome ◽

Single Nucleotide ◽

Androgen Insensitivity ◽

Complete Form ◽

Hormone Binding Domain

Complete androgen insensitivity syndrome is caused by X chromosome linked disorder resulting in a target organ insensitivity to androgen. Two variants have been described in this syndrome. In the first, the binding of [3H] dihydrotestosterone(17β-hydroxy-5α-androstan-3-one) to the androgen receptor is undetectable (receptor-negative), whereas in the second variant normal levels of androgen receptor are detectable but the binding of [3H] dihydrotesterone to the androgen receptor is significantly thermolabile under certain conditions (receptor-positive). In receptor-negative cases, genetic disorders of the androgen receptor gene have been demonstrated. On the other hand, the genetic disorder of androgen receptor in receptor-positive cases is little known. In this study, the gene structure of androgen receptor in a receptor-positive case using a polymerase chain reaction technique is studied in the fibroblasts cultured from genital skin. The results demonstrate that the substitution of nucleotide (guanine→cytosine) in exon G of the androgen receptor causes the replacement of an amino acid in position 820 (glycine→alanine) which occurs in the hormone-binding domain of the androgen receptor. The substitution of nucleotide may explain the thermolability of the androgen receptor in a case with receptor-positive androgen insensitivity syndrome.

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