Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity.
A locus on chromosome 15q25.1 previously implicated in nicotine, alcohol, and cocaine dependence, smoking, and lung cancer encodes subunits of the nicotinic acetylcholine receptor (nAChR) expressed in the mesolimbic system and thought to mediate substance dependence. Opioid dependence severity (ODS), nicotine dependence severity (NDS), smoking status and quantity, and the number of attempts to quit were assessed using questionnaire instruments in 505 subjects who were prescribed opioid medications for chronic pain in outpatient practice sites. Multivariate regression was used to test for genetic association of these phenotypes with 5 SNPs in the nAChR gene cluster on chromosome 15q25.1, adjusting for background variables. A coding variant in CHRNA5 (rs16969968[A]) was significantly associated with 1.4-unit higher ODS (p < 0.00017). A variant in the 3' untranslated region of CHRNA3 (rs660652[G]) was significantly associated with 1.7-fold higher odds of lifetime smoking (p < 0.0092), 1.1-unit higher NDS (p < 0.0007), 0.7 more pack-years of cigarette smoking (p < 0.0038), and 0.8 more lifetime attempts to quit (p < 0.0084). Our data suggest an association of DNA variants in the nAChR gene cluster on chromosome 15q25.1 with ODS, as well as NDS and related smoking phenotypes. While the association of this locus with NDS and smoking phenotypes is well known, the association with ODS, a dimension of opioid substance dependence, is novel and requires verification in independent studies.
Erlich
Porat M
PM
Center for Health Research, Geisinger Health System, 100 N Academy Avenue, Danville, PA 17822-4400, USA.
Hoffman
Stuart N
SN
Rukstalis
Margaret
M
Han
John J
JJ
Chu
Xin
X
Linda Kao
W H
WH
Gerhard
Glenn S
GS
Stewart
Walter F
WF
Boscarino
Joseph A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002884:Chromosomes, Human, Pair 15; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D009293:Opioid-Related Disorders / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055553:Prescription Drugs; D011978:Receptors, Nicotinic / Q000235:genetics*; D012720:Severity of Illness Index; D012907:Smoking; D016540:Smoking Cessation / Q000706:statistics & numerical data; D011795:Surveys and Questionnaires; D014029:Tobacco Use Disorder / Q000235:genetics*
D055553:Prescription Drugs; D011978:Receptors, Nicotinic