2004 - 2005 Publications >Genetics of Nicotine Addiction

Genetics of Nicotine Addiction

• A Significant LOD score of 3.30 was observed by Bierut et al on chromosome 2 for habitual smoking and alcoholism.  Modest linkage for habitual smoking was found on chromosomes 5, 9, 11, and 21. This suggests that there may be a common genetic vulnerability locus for habitual smoking and alcoholism as well as specific vulnerability loci for nicotine dependence.  Am J Med Genet A. 2004 Jan 1;124(1):19-27
• Faraone et al (Harvard Medical School) have shown association of the alpha2 nicotinic receptor and the beta2 nicotinic receptor to schizophrenia and smoking.  Hum Hered. 2004;57(2):59-68
• Gelernter et al identified evidence for two loci increasing risk for cigarette smoking that map to chromosomes 9 and 11. Genetic locifor chromosome 9 has also been linked to panic disorder in an Icelandic co-hort.  Am J Med Genet. 2004 Jul 1;128B(1):94-101
• Lessov et al reported that DSM-IV criteria of tolerance, withdrawal, and experiencing difficulty quitting and HSI items time to first cigarette in the morning and number of cigarettes smoked per day may represent the most highly heritable symptoms of nicotine dependence for both women and men  Psychol Med. 2004 Jul;34(5):865-79 by the 11th grade increased almost twofold with each additional DRD2 A1 allele. The likelihood of smoking progression with each additional A1 allele was more pronounced among adolescents with substantial depression symptoms. Am J Psychiatry. 2004 Jul;161(7):1224-30
• Schoedel et al  found that low nicotine inactivators who have a less active form of CYP2A6 are less likely to be adult smokers (dependent or non-dependent). Slow inactivators also smoked fewer cigarettes per day and had an earlier age of first smoking (only dependent smokers).  Pharmacogenetics. 2004 Sep;14(9):615-26
• Salas et al reported that 4 subunit of nAChRs is critical for nicotine withdrawal symptoms in mice, whereas the deletion of b2 subunit does not affect withdrawal The Journal of Neuroscience, November 10, 2004, 24(45):10035-10039  
• Tapper et al created a knockin mouse in which the alpha 4 subunit was engineered to be sensitive to nicotine.  This study showed that the alpha 4 variant is sufficient to mediate the actions of nicotine on reward, tolerance, and sensitization nicotine.  Science. 2004 Nov 5;306(5698):1029-32. Human data suggests that variants of alpha4 may be protective (Feng et al  Am J. Hum. Genet 75:112, 2004)
• Li et al show significant association of alpha 4 nicotinic  receptor gene variants for nicotine dependence in African American and European Americans. Hum Mol Genet. 2005 May 1;14(9):1211-9.
• Beuten et al  showed that gene variants of the GABAB2 receptor are associated with nicotine dependence.  GABAB2 receptor gene is located with a region of chromosome 9q22 that showed a possible linkage to nicotine dependence.  Am J Hum Genet. 2005 May;76(5):859-64
• Zhang et al  have identified PTEN (phosphatase and tensin homolog gene) with smoking initiation and cigarette consumption.  This candidate gene falls within 10q23 chromosomal linkage peak in a genome scan for cigarette consumption and smoking initiation. Am J Med Genet B Neuropsychiatr Genet. 2006 Jan 5;141(1):10-4. 
• Mexal et al shows that gene encoding proteins that are expressed at the NMDA receptor post-synaptic density complex are upregulated in schizophrenic and normal smokers. Brain Res Mol Brain Res 2005 139(2): 317-32.
• Lerman and her colleagues report that buprion therapy for the treatment of nicotine dependence was more effective in individuals homozygous for a insertion at the 141 C allele of the DRD2 receptor than those carrying a deletion of the 141 C allele.  Conversely, those carrying the 141 C deletion allele of the DRD2 receptor have a much higher quit rate in response to nicotine replacement therapy than those carrying the 141 C insertion allele.  Neuropsychopharmacology. 2006 Jan;31(1):231-42.
• Beuten et al found that COMT is associated with nicotine dependence.  Low enzyme activity met allele of COMT was protective from becoming dependent. Neuropsychopharmacology. 2005 Dec 14; and that Colila et al shows that the Met/Met allele of COMT is associated with increase smoking cessation following nicotine replacement therapy.  Pharmacogenet Genomics. 2005 Jun;15(6):393-8.
• Haplotype analysis by Ma et al indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence. Hum Mol Genet. 2005 Jun 15;14(12):1691-8.
• Swan et al after controlling for the genetic contribution of known CYP2A6 alleles on nicotine metabolism found that significant genetic factors remained for clearing nicotine.  These results suggest that other genes or alleles of CYP2A6 contribute to nicotine metabolism.  Pharmacogenet Genomics. 2005 Feb;15(2):115-25
• Mice carrying a polymorphism of the alpha 4 subunit of the nicotinic acetylcholine receptor (AchR) in which threonine is substituted for an alanine at amino acid 527 in the alpha 4 subunit show increased consumption and preference for both alcohol and nicotine.  Work by Al Collins and his colleagues show that the mouse Chrna4 A529T polymorphism explains nicotine preference but not alcohol preference, suggesting that a gene closely linked to Chrna4 mediates the increased alcohol consumption. Butt et al  Behav Neurosci. 2005 Feb;119(1):26-37
• Francis et al showed that The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic transmission at the C. elegans neuromuscular junction. ACR-16 is homolgous to the nicotine alpha 7 receptor subunit in mammals. Neuron. 2005 May 19;46(4):581-94
• Tyrosine phosphorylation regulates alpha7 nictotinic acetylcholine receptors Cho et al  J Neurosci. 2005 Apr 6;25(14):3712-23
• McIntosh et al  Identified a novel peptide that can be used to distinguish between nicotinic acetylcholine receptors J Biol Chem. 2005 Aug 26;280(34):30107-12