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

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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.

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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

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Acknowledgments

This work was supported by a grant from the Administrative Committee for Research (ACR), Geisinger Clinic, Grant No. TRA-015 to Dr. Boscarino. Preliminary results for this study were presented at the 15th Annual HMO Research Network Conference, Danville, PA, April, 2009.

Conflict of interest

The authors have no conflicts of interest related to this research.

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Authors and Affiliations

  1. Center for Health Research, Geisinger Health System, 100 N. Academy Avenue, Danville, PA, 17822-4400, USA

    Porat M. Erlich, Margaret Rukstalis, Walter F. Stewart & Joseph A. Boscarino

  2. Department of Medicine, Temple School of Medicine, Philadelphia, PA, USA

    Porat M. Erlich

  3. Department of Neurology, Geisinger Health System, Danville, PA, USA

    Stuart N. Hoffman

  4. Department of Pain Medicine, Geisinger Health System, Danville, PA, USA

    John J. Han

  5. Weis Center, Geisinger Health System, Danville, PA, USA

    Xin Chu & Glenn S. Gerhard

  6. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    W. H. Linda Kao & Walter F. Stewart

  7. Department of Medicine and Pediatrics, Mt Sinai School of Medicine, New York, NY, USA

    Joseph A. Boscarino

  8. Department of Psychiatry, Temple School of Medicine, Philadelphia, PA, USA

    Joseph A. Boscarino

Authors
  1. Porat M. Erlich
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  2. Stuart N. Hoffman
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  3. Margaret Rukstalis
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  4. John J. Han
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  5. Xin Chu
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  6. W. H. Linda Kao
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  7. Glenn S. Gerhard
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  8. Walter F. Stewart
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  9. Joseph A. Boscarino
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Corresponding author

Correspondence to Joseph A. Boscarino.

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Erlich, P.M., Hoffman, S.N., Rukstalis, M. et al. Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity. Hum Genet 128, 491–499 (2010). https://doi.org/10.1007/s00439-010-0876-6

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  • DOI: https://doi.org/10.1007/s00439-010-0876-6

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