title: Association between polymorphism of the dopamine transporter gene and early smoking onset: an interaction risk on nicotine dependence.
abstract: Previous studies suggested that a polymorphism in the dopamine transporter gene (SLC6A3) is associated with nicotine dependence and age of smoking onset, but the conclusion was controversial. To detect the association of a G-->A polymorphism (NCBI dbSNP cluster ID: rs27072) in 3'-untranslated region of the SLC6A3 with nicotine dependence and early smoking onset, we recruited 253 sibships including 668 nicotine-dependent siblings from a rural district of China. The sibship disequilibrium tests (SDT) showed that the rs27072-A allele is significantly associated with smoking onset < or =18 years (kappa2=9.78, p=0.003 in severely nicotine-dependent smokers, and kappa2=4.24, p=0.058 in total smokers), but not significantly associated with severe nicotine dependence. Conditional logistic regression showed that the risk of early smoking onset by the rs27072-A allele was almost three times greater in severely nicotine-dependent smokers [Odds ratio (OR)=11.3, 95% confidence interval (CI)=1.5-85.6] than that in total smokers. Linear regression showed that rs27072-A allele also increased the risk of nicotine dependence by early smoking onset compared with homozygous rs27072-G genotype. Although these findings are preliminary and need validation, the results suggest that a polymorphism in the SLC6A3 may play important roles in smoking onset, and there may be an interactive effect between the SLC6A3 and early smoking onset on modulating the susceptibility of nicotine dependence.
authors.affiliation: School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Daijun
authors.initials: D
authors.lastname: Ling
authors.affiliation: Program for Population Genetics, Harvard School of Public Health, Harvard University, Boston, MA, USA.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Niu
authors.affiliation: Program for Population Genetics, Harvard School of Public Health, Harvard University, Boston, MA, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Program for Population Genetics, Harvard School of Public Health, Harvard University, Boston, MA, USA.
authors.forename: Houxun
authors.initials: H
authors.lastname: Xing
authors.affiliation: School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China. xu@hsph.harvard.edu.|Program for Population Genetics, Harvard School of Public Health, Harvard University, Boston, MA, USA. xu@hsph.harvard.edu.
authors.forename: Xiping
authors.initials: X
authors.lastname: Xu
mesh_terms: D017668:Age of Onset; D000483:Alleles; D002681:China; D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*
chemical_list: D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human