Association of CHRN genes with "dizziness" to tobacco.
The neuronal nicotinic receptor genes (CHRN) have been implicated in a variety of smoking-related behaviors. Here we tested for association between an early subjective response phenotype, "dizziness," and 226 single nucleotide polymorphisms (SNPs) in CHRN genes. The sample included 789 nicotine-dependent cases and 811 controls, where early "dizziness" reports were significantly associated with case/control status (P < 0.0001). Multiple SNPs in the putative promoter region of the CHRNB3 gene were nominally associated with "dizziness" experience from the first few cigarettes (P < 0.01). Cell culture studies were conducted to examine the ability of different haplotypes in the CHRNB3 promoter to drive luciferase expression. Data from these experiments support the hypothesis that different alleles in the CHRNB3 upstream promoter region may lead to different levels of RNA expression. In addition, a novel finding of association between SNPs in the CHRNA10 gene reached experiment-wide empirical significance (P = 0.048), which implicates another CHRN gene as being involved in early subjective response to tobacco.
Ehringer
Marissa A
MA
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado.|Department of Integrative Physiology, University of Colorado, Boulder, Colorado.
McQueen
Matthew B
MB
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado.|Department of Integrative Physiology, University of Colorado, Boulder, Colorado.
Hoft
Nicole R
NR
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado.
Saccone
Nancy L
NL
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri.
Stitzel
Jerry A
JA
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado.|Department of Integrative Physiology, University of Colorado, Boulder, Colorado.
Wang
Jen C
JC
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
Bierut
Laura J
LJ
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
D000328:Adult; D016022:Case-Control Studies; D004244:Dizziness; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking; D014026:Nicotiana
C493739:CHRNA10 protein, human; D011978:Receptors, Nicotinic; D012313:RNA