Karahalil B, Coskun E, Emerce E
Department of Toxicology, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
Toxicol Ind Health. 2008 Apr;24(3):171-6. doi: 10.1177/0748233708093354.
Adrenoceptors (ARs) consist of nine subtypes, which are involved in a wide spectrum of physiological functions and are the site of action for a considerable percentage of currently prescribed therapeutics. All AR subtypes (except alpha(1D)) can be polymorphic because of the genetic variations in the coding and non-coding regions. Sixteen sequence variations were identified in alpha-adrenergic 2A (ADRA2A) gene. Among them, ADRA2A C1291G polymorphism is one of the most important polymorphisms, which plays a major role in regulating neurotransmitter release, blood pressure, lipolysis, insulin secretion, and platelet aggregation. A C-G transversion results in an MspI restriction fragment length polymorphism located at 1291 bp upstream of the origin of transcription. Because Medline search showed no study showing the allelic frequencies, and no information is available on inter-individual variability of ADRA2A C1291G polymorphism in Turkish population, we genotyped 203 healthy Turkish subjects. Because of large genetic variation of the polymorphism, we aimed to find out the distribution of C1291G polymorphism in Turkish population. Furthermore, we evaluated the possible association between the C1291G polymorphism in the ADRA2A receptor gene and smoking. The frequencies for the 1291C and 1291G alleles were 64% and 36%, respectively. The genotype frequencies for C1291C, C1291G, and G1291G were 35.5%, 57.6%, and 6.9%, respectively, in Turkish population. The allelic frequencies (1291C and 1291G) and G1291G homozygous variant genotype were similar to those reported in different Caucasian populations; however, C1291C and C1291G genotypes were different. We also observed that the frequency of the G allele was slightly higher in smoker subjects and lower among controls. The ADRA2A G allele may play a role in the predisposition to smoking. There is a need for expanding genotype and haplotype studies because of its importance in various physiological disorders and to confirm the association of this polymorphism with smoking.
肾上腺素能受体(ARs)由九种亚型组成,它们参与广泛的生理功能,并且是目前相当一部分处方药的作用位点。由于编码区和非编码区的基因变异,所有AR亚型(α1D除外)都可能具有多态性。在α-肾上腺素能2A(ADRA2A)基因中鉴定出16种序列变异。其中,ADRA2A C1291G多态性是最重要的多态性之一,它在调节神经递质释放、血压、脂肪分解、胰岛素分泌和血小板聚集方面起主要作用。C-G颠换导致位于转录起始点上游1291 bp处的MspI限制性片段长度多态性。由于医学文献检索显示没有研究表明等位基因频率,并且没有关于土耳其人群中ADRA2A C1291G多态性个体间变异性的信息,我们对203名健康的土耳其受试者进行了基因分型。由于该多态性存在较大的遗传变异,我们旨在了解C1291G多态性在土耳其人群中的分布。此外,我们评估了ADRA2A受体基因中C1291G多态性与吸烟之间可能的关联。1291C和1291G等位基因的频率分别为64%和36%。在土耳其人群中,C1291C、C1291G和G1291G基因型频率分别为35.5%、57.6%和6.9%。等位基因频率(1291C和1291G)以及G1291G纯合变异基因型与不同高加索人群报道的相似;然而,C1291C和C1291G基因型不同。我们还观察到,吸烟者中G等位基因的频率略高,而在对照组中较低。ADRA2A G等位基因可能在吸烟易感性中起作用。由于其在各种生理疾病中的重要性以及确认这种多态性与吸烟的关联,有必要扩大基因型和单倍型研究。