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Association of a Novel Polymorphism of the β2-Chimaerin Gene (CHN2) With Smoking
  1. Laura Barrio-Real, PhD*,
  2. Miguel Barrueco, MD, PhD*,
  3. Rogelio González-Sarmiento, MD, PhD*,
  4. María J. Caloca, PhD
  1. From the *Unidad de Medicina Molecular, Facultad de Medicina, Hospital Universitario de Salamanca and IBMCC (CSIC/Universidad de Salamanca), Salamanca, Spain; and †Instituto de Biología y Genética Molecular (IBGM), Consejo Superior de Investigaciones Científicas (CSIC), Valladolid. Spain.
  1. Received April 25, 2013, and in revised form June 14, 2013.
  2. Accepted for publication June 25, 2013.
  3. Reprints: Rogelio González-Sarmiento, MD, PhD, and María J. Caloca, PhD, Instituto de Biología y Genética Molecular (IBGM), c/ Sanz y Forés s/n, 47003 Valladolid, Spain. E-mail: mj.caloca{at}
  4. Supported by Spanish Ministry of Health (Fondo de Investigaciones Sanitarias, PI052096 to MJC, PI10/00219 to RGS), the Spanish Ministry of Science and Innovation cosponsored by the plan E (BFU2009-08051 to MJC), and the Castilla y Leon Autonomous Government (BIO103/VA44/11 to MJC and GR15 to RGS).


Objective The CHN2 gene encodes the β2-chimaerin, a Rac-specific guanosine-5′-triphosphatase activating protein with an important role in the establishment of functional brain circuitry by controlling axon pruning. Genetic studies suggest that the CHN2 gene harbors variants that contribute to addiction vulnerability and smoking behavior. To further evaluate the role of β2-chimaerin in nicotine addiction, we investigated the association of 3 individual polymorphisms of the CHN2 gene with smoking dependence.

Methods Three hundred sixty-one healthy volunteers, 173 smokers (mean ± SD age, 60.4 ± 1.4 years) and 188 control subjects (mean ± SD age, 45.9 ± 1.4 years) were genotyped for 3 single-nucleotide polymorphisms in the CHN2 gene (rs3750103, rs12112301, and rs186911567). The association of these polymorphisms with smoking habits was analyzed.

Results There was no significant association of polymorphisms rs12112301 and rs3750103 with smoking. However, there was a significant difference in the frequency of the rs186911567 polymorphism between the smokers and the controls (P = 0.003).

Conclusions We report for the first time a significant association of the novel rs186911567 polymorphism of the CHN2 gene with smoking.

Key Words
  • β2-chimaerin
  • CHN2
  • addiction
  • polymorphisms
  • smoking

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