Genetic influences on nicotinic 伪5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue

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• 作者：Jessica E. Ramsay ; C. Harker Rhodes ; Keerthi Thirtamara-Rajamani…
• 关键词：Nicotinic receptors ; Nicotine ; mRNA expression ; Enhancer ; Repressor ; Silencer ; Methylation ; Epigenetics ; Expression quantitative trait loci ; eQTL ; Functional polymorphism ; Allelic expression
• 刊名：Genes and Environment
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：37
• 期：1
• 全文大小：1737KB
• 参考文献：1.Saccone NL, Culverhouse RC, Schwantes-An TH, Cannon DS, Chen X, Cichon S, et al. Multiple independent loci at chromosome 15q25.1 affect smoking quantity: A meta-analysis and comparison with lung cancer and COPD. PLoS Genet. 2010;6, e1001053.PubMed Central PubMed CrossRef
  2.Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA, et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Gen. 2007;16:36鈥?9.PubMed Central PubMed CrossRef
  3.Berrettini W, Yuan X, Tozzi F, Song K, Francks C, Chilcoat H, et al. Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking. Mol Psychiatry. 2008;13:368鈥?3.PubMed Central PubMed CrossRef
  4.Schlaepfer IR, Hoft NR, Collins AC, Corley RP, Hewitt JK, Hopfer CJ, et al. The CHRNA5/A3/B4 gene cluster variability as an important determinant of early alcohol and tobacco initiation in young adults. Biol Psychiatry. 2008;63:1039鈥?6.PubMed Central PubMed CrossRef
  5.Wang JC, Cruchaga C, Saccone NL, Bertelsen S, Liu P, Budde JP, et al. Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Hum Mol Gen. 2009;18:3125鈥?5.PubMed Central PubMed CrossRef
  6.Wang JC, Grucza R, Cruchaga C, Hinrichs AL, Bertelsen S, Budde JP, et al. Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence. Mol Psychiatry. 2009;14:501鈥?0.PubMed Central PubMed CrossRef
  7.Erlich PM, Hoffman SN, Rukstalis M, Han JJ, Chu X, Linda Kao WH, et al. Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity. Hum Genet. 2010;128:491鈥?.PubMed CrossRef
  8.Sherva R, Kranzler HR, Yu Y, Logue MW, Poling J, Arias AJ, et al. Variation in nicotinic acetylcholine receptor genes is associated with multiple substance dependence phenotypes. Neuropsychopharmacology. 2010;35:1921鈥?1.PubMed Central PubMed CrossRef
  9.Smith RM, Alachkar H, Papp AC, Wang D, Mash DC, Wang JC, et al. Nicotinic alpha5 receptor subunit mRNA expression is associated with distant 5' upstream polymorphisms. Eur J Hum Genet. 2011;19:76鈥?3.PubMed Central PubMed CrossRef
  10.Grucza RA, Wang JC, Stitzel JA, Hinrichs AL, Saccone SF, Saccone NL, et al. A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence. Biol Psychiatry. 2008;64:922鈥?.PubMed Central PubMed CrossRef
  11.Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet. 2008;40:616鈥?2.PubMed Central PubMed CrossRef
  12.Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008;452:633鈥?.PubMed CrossRef
  13.Wilk JB, Shrine NR, Loehr LR, Zhao JH, Manichaikul A, Lopez LM, et al. Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction. Am J Respir Crit Care Med. 2012;186:622鈥?2.PubMed Central PubMed CrossRef
  14.Bierut LJ, Stitzel JA, Wang JC, Hinrichs AL, Grucza RA, Xuei X, et al. Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry. 2008;165:1163鈥?1.PubMed Central PubMed CrossRef
  15.Morel C, Fattore L, Pons S, Hay YA, Marti F, Lambolez B, et al. Nicotine consumption is regulated by a human polymorphism in dopamine neurons. Mol Psychiatry. 2014;19:930鈥?.PubMed CrossRef
  16.Fowler CD, Lu Q, Johnson PM, Marks MJ, Kenny PJ. Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake. Nature. 2011;471:597鈥?01.PubMed Central PubMed CrossRef
  17.Salas R, Orr-Urtreger A, Broide RS, Beaudet A, Paylor R, De Biasi M. The nicotinic acetylcholine receptor subunit alpha 5 mediates short-term effects of nicotine in vivo. Mol Pharmacol. 2003;3:1059鈥?6.CrossRef
  18.Hsu YW, Tempest L, Quina LA, Wei AD, Zeng H, Turner EE. Medial habenula output circuit mediated by alpha5 nicotinic receptor-expressing gabaergic neurons in the interpeduncular nucleus. J Neurosci. 2013;33:18022鈥?5.PubMed Central PubMed CrossRef
  19.Bianco IH, Wilson SW. The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philos Trans R Soc Lond B Biol Sci. 2009;364:1005鈥?0.PubMed Central PubMed CrossRef
  20.Chatterjee S, Santos N, Holgate J, Haass-Koffler CL, Hopf FW, Kharazia V, et al. The 伪5 subunit regulates the expression and function of 伪4*-containing neuronal nicotinic acetylcholine receptors in the ventral-tegmental area. PLoS One. 2014;8, e68300.CrossRef
  21.Moyer RA, Wang D, Papp AC, Smith RM, Duque L, Mash DC, et al. Intronic polymorphisms affecting alternative splicing of human dopamine D2 receptor are associated with cocaine abuse. Neuropsychopharmacology. 2011;36:753鈥?2.PubMed Central PubMed CrossRef
  22.Di Giorgio A, Smith RM, Fazio L, D鈥橝mbrosio E, Gelao B, Tomasicchio A, et al. DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory. PLoS One. 2014;9, e95997.PubMed Central PubMed CrossRef
  23.Doyle GA, Wang MJ, Chou AD, Oleynick JU, Arnold SE, Buono RJ, et al. In vitro and ex vivo analysis of chrna3 and chrna5 haplotype expression. PLoS One. 2011;6, e23373.PubMed Central PubMed CrossRef
  24.Numata S, Ye T, Hyde TM, Guitart-Navarro X, Tao R, Wininger M, et al. DNA methylation signatures in development and aging of the human prefrontal cortex. Am J Hum Genet. 2012;90:260鈥?2.PubMed Central PubMed CrossRef
  25.Grundberg E, Meduri E, Sandling JK, Hedman 脜K, Keildson S, Buil A, et al. Global analysis of DNA methylation variation in adipose tissue from twins reveals links to disease-associated variants in distal regulatory elements. Am J Hum Genet. 2013;93:876鈥?0.PubMed Central PubMed CrossRef
  26.Zhang H, Wang F, Kranzler HR, Zhao H, Gelernter J. Profiling of childhood adversity-associated DNA methylation changes in alcoholic patients and healthy controls. PLoS One. 2013;8, e65648.PubMed Central PubMed CrossRef
  27.Xie P, Kranzler HR, Zhang H, Oslin D, Anton RF, Farrer LA, et al. Childhood adversity increases risk for nicotine dependence and interacts with alpha5 nicotinic acetylcholine receptor genotype specifically in males. Neuropsychopharmacology. 2012;37:669鈥?6.PubMed Central PubMed CrossRef
  28.Colantuoni C, Lipska BK, Ye T, Hyde TM, Tao R, Leek JT, et al. Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature. 2011;478:519鈥?3.PubMed Central PubMed CrossRef
  29.Grundberg E, Small KS, Hedman 脜K, Nica AC, Buil A, Keildson S, et al. Mapping cis and trans regulatory effects across multiple tissues in twins. Nat Genet. 2012;44:1084鈥?.PubMed Central PubMed CrossRef
  30.Guintivano J, Aryee MJ, Kaminsky ZA. A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression. Epigenetics. 2013;8:290鈥?02.PubMed Central PubMed CrossRef
  31.Han ZY, Le Novere N, Zoli M, Hill Jr JA, Champtiaux N, Changeux JP. Localization of nAChR subunit mRNAs in the brain of macaca mulatta. Eur J Neurosci. 2000;12:3664鈥?4.PubMed CrossRef
  32.Westra HJ, Peters MJ, Esko T, Yaghootkar H, Schurmann C, Kettunen J, et al. Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat Genet. 2013;45:1238鈥?3.PubMed Central PubMed CrossRef
  33.Zeller T, Wild P, Szymczak S, Rotival M, Schillert A, Castagne R, et al. Genetics and beyond 鈥?The transcriptome of human monocytes and disease susceptibility. PLoS One. 2010;5, e10693.PubMed Central PubMed CrossRef
  34.Hao K, Boss茅 Y, Nickle DC, Par茅 PD, Postma DS, Laviolette M, et al. Lung eQTLs to help reveal the molecular underpinnings of asthma. PLoS Genet. 2012;8, e1003029.PubMed Central PubMed CrossRef
  35.Rosenbloom KR, Sloan CA, Malladi VS, Dreszer TR, Learned K, Kirkup VM, et al. Encode data in the UCSC genome browser: Year 5 update. Nucleic Acids Res. 2013;41:D56鈥?3.PubMed Central PubMed CrossRef
  36.Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, et al. The human genome browser at UCSC. Genome Res. 2002;12:996鈥?006.PubMed Central PubMed CrossRef
  37.Schoenherr CJ, Anderson DJ. The neuron-restrictive silencer factor (NRSF): A coordinate repressor of multiple neuron-specific genes. Science. 1995;267:1360鈥?.PubMed CrossRef
  38.Bessis A, Champtiaux N, Chatelin L, Changeux JP. The neuron-restrictive silencer element: A dual enhancer/silencer crucial for patterned expression of a nicotinic receptor gene in the brain. Proc Natl Acad Sci U S A. 1997;94:5906鈥?1.PubMed Central PubMed CrossRef
  39.Seth KA, Majzoub JA. Repressor element silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) can act as an enhancer as well as a repressor of corticotropin-releasing hormone gene transcription. J Biol Chem. 2001;276:13917鈥?3.PubMed
  40.Rebeiz M, Pool JE, Kassner VA, Aquadro CF, Carroll SB. Stepwise modification of a modular enhancer underlies adaptation in a drosophila population. Science. 2009;326:1663鈥?.PubMed Central PubMed CrossRef
  41.Rebeiz M, Jikomes N, Kassner VA, Carroll SB. Evolutionary origin of a novel gene expression pattern through co-option of the latent activities of existing regulatory sequences. Proc Natl Acad Sci U S A. 2011;108:10036鈥?3.PubMed Central PubMed CrossRef
  42.Curradi M, Izzo A, Badaracco G, Landsberger N. Molecular mechanisms of gene silencing mediated by DNA methylation. Mol Cell Biol. 2002;22:3157鈥?3.PubMed Central PubMed CrossRef
  43.Salas R, Sturm R, Boulter J, De Biasi M. Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice. J Neurosci. 2009;29:3014鈥?.PubMed Central PubMed CrossRef
  44.Klink R, de Kerchove d'Exaerde A, Zoli M, Changeux JP. Molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei. J Neurosci. 2001;21:1452鈥?3.PubMed
  45.Russo SJ, Nestler EJ. The brain reward circuitry in mood disorders. Nat Rev Neurosci. 2013;14:609鈥?5.PubMed CrossRef
  46.Schwantes-An TH, Culverhouse R, Duan W, Ramnarine S, Rice JP, Saccone NL. Interpreting joint SNP analysis results: When are two distinct signals really two distinct signals? Genet Epidemiol. 2013;37:301鈥?.PubMed Central PubMed CrossRef
  
• 作者单位：Jessica E. Ramsay (1) (2)
  C. Harker Rhodes (3)
  Keerthi Thirtamara-Rajamani (2)
  Ryan M. Smith (1) (2)
  
  1. Center for Pharmacogenomics, The Ohio State University, Columbus, OH, 43210, USA
  2. Department of Pharmacology, The Ohio State University, 5184A Graves Hall, 333. W. 10th Ave., Columbus, OH, 43210, USA
  3. National Institute of Mental Health, Human Brain Collection Core, 10 Center Drive, Rm. 4N306, Bethesda, MD, USA
  
• 刊物类别：Human Genetics;
• 刊物主题：Human Genetics;
• 出版者：BioMed Central
• ISSN：1880-7062

文摘

Introduction The nicotinic 伪5 receptor subunit, encoded by CHRNA5, harbors multiple functional single nucleotide polymorphisms (SNPs) that affect mRNA expression and alter the encoded protein. These polymorphisms are most notably associated with drug-taking behaviors and cognition. We previously identified common SNPs in a distant regulatory element (DRE) that increase CHRNA5 mRNA expression in the human prefrontal cortex (PFC) and confer risk for nicotine dependence. Genome-wide epigenetic studies in PFC and adipose tissue find strong effects of the DRE SNPs on CpG methylation. However, it is unclear whether DRE SNPs influence CpG methylation en route to modulating CHRNA5 mRNA expression. It is also unclear whether these polymorphisms affect expression in other brain regions, especially those mediating drug-taking behaviors.