Identification of a novel 12-nucleotide insertion polymorphism in the promoter region of ADRA2B: Full linkage with the 9-nucleotide deletion in the coding region and influence on transcriptional activity

Abstract

, et al.. Identification of a novel 12-nucleotide insertion polymorphism in the promoter region of ADRA2B: full linkage with the 9-nucleotide deletion in the coding region and influence on transcriptional activity. Biochemical Pharmacology, Elsevier, 2009, 79 (3) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

Lack of association between ADRA2B -4825 gene insertion/deletion polymorphism and migraine in Chinese Han population

“…The present case-control association study indicates that ADRA2B -4825 indel polymorphism is not associated with migraine, which is consistent with a previous report [7] . Since the -4825 indel polymorphism is in complete linkage with the indel polymorphism at position +901 and a G/C substitution at position -98 [9] , combined with previously reported data for female migraine subjects [8] , our findings do not support a major role of the polymorphisms within adrenergic receptor systems in migraine pathology.…”

“…More recently, a population study has identified a novel 12-nucleotide (GGGACGGCCCTG) insertion/deletion (indel) polymorphism at position -4825 relative to the start codon in the far upstream region of the ADRA2B promoter (-4825 indel). Besides, this indel polymorphism is shown to be common and in complete linkage with the deletion polymorphism at position +901 and a G/C substitution at position -98 [9] . The present study was aimed to investigate whether the 12-bp indel polymorphism is associated with migraine in Chinese Han population.…”

Genetic Variations of α2-Adrenergic Receptors Illuminate the Diversity of Receptor Functions

“…The impact of a 2B AR Del301-303 observed varies based on a number of factors, particularly the ethnic makeup of the sample population. As well, given that the Del301-303 polymorphism is in linkage with other a 2B AR polymorphisms in certain populations (Cayla et al, 2004;Etzel et al, 2005;Crassous et al, 2010), it is possible that there are complex effects of the a 2B AR genotype. As an example, the Del301-303 polymorphism may result in enhanced receptor signaling while a noncoding polymorphism such as the 5 0 -UTR deletion beginning at position -4825 may lead to decreased receptor expression.…”

“…Interestingly, these five polymorphisms listed above have been found to be in linkage with each other, especially in the Caucasian population (Cayla et al, 2004;Etzel et al, 2005;Crassous et al, 2010). At the molecular level, the noncoding region polymorphisms may have effects on transcriptional activity at the a 2B AR gene, thereby affecting receptor expression levels (Cayla et al, 2004).…”

“…Other relatively common polymorphisms are found in noncoding regions, and include a 12 nucleotide deletion beginning at position -4825 in the 5 0 -UTR (Crassous et al, 2010), a G-98C SNP in the 5 0 -UTR (Cayla et al, 2004), a synonymous coding region mutation at position 1182 (Etzel et al, 2005), and a C1776A SNP in the 3 0 -UTR. Interestingly, these five polymorphisms listed above have been found to be in linkage with each other, especially in the Caucasian population (Cayla et al, 2004;Etzel et al, 2005;Crassous et al, 2010).…”