Human Genetics

, Volume 128, Issue 5, pp 491–499

Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity

  • Porat M. Erlich
  • Stuart N. Hoffman
  • Margaret Rukstalis
  • John J. Han
  • Xin Chu
  • W. H. Linda Kao
  • Glenn S. Gerhard
  • Walter F. Stewart
  • Joseph A. Boscarino
Original Investigation

DOI: 10.1007/s00439-010-0876-6

Cite this article as:
Erlich, P.M., Hoffman, S.N., Rukstalis, M. et al. Hum Genet (2010) 128: 491. doi:10.1007/s00439-010-0876-6

Abstract

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.

Abbreviations

LD

Linkage disequilibrium

PCR

Polymerase chain reaction

MAF

Minor allele frequency

ODS

Opioid dependence severity

SDS

Severity of dependence scale

NDS

Nicotine dependence severity

FTS

Fagerstrom tolerance scale

EHR

Electronic health record

nAChR

Nicotinic acetylcholine receptor

CHRNA

Cholinergic receptor nicotinic alpha

SNP

Single nucleotide polymorphism

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Porat M. Erlich
    • 1
    • 2
  • Stuart N. Hoffman
    • 3
  • Margaret Rukstalis
    • 1
  • John J. Han
    • 4
  • Xin Chu
    • 5
  • W. H. Linda Kao
    • 6
  • Glenn S. Gerhard
    • 5
  • Walter F. Stewart
    • 1
    • 6
  • Joseph A. Boscarino
    • 1
    • 7
    • 8
  1. 1.Center for Health ResearchGeisinger Health SystemDanvilleUSA
  2. 2.Department of MedicineTemple School of MedicinePhiladelphiaUSA
  3. 3.Department of NeurologyGeisinger Health SystemDanvilleUSA
  4. 4.Department of Pain MedicineGeisinger Health SystemDanvilleUSA
  5. 5.Weis CenterGeisinger Health SystemDanvilleUSA
  6. 6.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  7. 7.Department of Medicine and PediatricsMt Sinai School of MedicineNew YorkUSA
  8. 8.Department of PsychiatryTemple School of MedicinePhiladelphiaUSA