Genetics of smoking behavior in American Indians

Jeffrey A Henderson 1, Dedra S Buchwald 2, Barbara V Howard 3, Patricia Nez Henderson 4, Yafang Li 5, Rachel F Tyndale 6, Christopher I Amos 5, Olga Y Gorlova 5

Affiliations

PMID: 32855268
DOI: 10.1158/1055-9965.EPI-20-0026

Abstract

Background: The smoking behavior of American Indians (AIs) differs from that of non-Hispanic whites (NHWs). Typically light smokers, cessation interventions for AIs are generally less effective. To improve cessation programs for AIs, clinicians, researchers and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether single nucleotide polymorphisms (SNPs) associated with smoking behavior in NHWs are also associated with smoking in AIs.

Methods: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in the Northern Plains (n=323) and the other in the Southwest (n=176). A total of 384 SNPs were genotyped using an Illumina custom GoldenGate platform. Samples were also assessed for cotinine and 3-hydroxycotinine as markers of nicotine intake and nicotine metabolite ratio.

Results: Among 499 participants, we identified, in the NP sample only, a variant of the gamma-aminobutyric acid receptor subunit alpha-2 (GABRA2) (rs2119767) on chromosome 4p that was associated with many of the intake biomarkers of smoking we examined, suggesting a role for this gene in modifying smoking behavior in this population. We also identified 3 SNPs, in the SW sample only, as significant correlates of only cigarettes per day: rs4274224, rs4245147 (both dopamine receptor D2 gene), and rs1386493 (tryptophan hydroxylase 2 gene).

Conclusions: The contribution of many genes known to underlie smoking behavior in NHWs may differ in AIs.

Impact: Once validated, these variants could be useful in developing more effective cessation strategies.