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PMID: 21073885 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

The α7 nicotinic acetylcholine receptor and the acute stress response: maternal genotype determines offspring phenotype.

Physiology & behavior ·Vol. 104 ·No. 2 ·2011-08-03 ·Pages 321-6

Sinkus ML, Wamboldt MZ, Barton A, Fingerlin TE, Laudenslager ML, Leonard S

Abstract

α7 Nicotinic acetylcholine receptors (α7nAchRs) modulate immune activation by suppressing production of pro-inflammatory cytokines in peripheral immune cells. α7nAchRs also modulate inhibitory output in the hippocampus, which provides input to key circuits of the HPA axis. Therefore, the α7 nicotinic acetylcholine receptor gene (CHRNA7) may be associated with cortisol stress response. Polymorphisms in the CHRNA7 promoter decrease its expression and may dampen the cholinergic response, leading to an increase in inflammation. Increased inflammation may change the intrauterine environment, altering neuroendocrine development in the offspring. Maternal CHRNA7 genotype could affect an offspring's HPA regulation via reprogramming in utero. Patients with allergic disorders have a differential cortisol response to stress. This study utilized samples collected from a cohort of 198 adolescents in a previous study of atopic disorders, who demonstrated a disturbance in HPA response associated with atopy. Salivary cortisol samples collected from the adolescents after a series of laboratory procedures and DNA samples collected from the adolescents and their parents were used for further analysis. DNA samples were genotyped for allelic variation in the CHRNA7 promoter. Genetic association analyses with the cortisol levels were performed in the adolescents. Maternal genotype influences were investigated for the CHRNA7 gene. We also included maternal and child atopy diagnosis as covariates in determining cortisol levels and tested for association of CHRNA7 to atopy. Polymorphisms in the CHRNA7 promoter were associated with lower cortisol levels after a small laboratory stress. Our findings also show that although the child's CHRNA7 genotype affects stress response, the maternal genotype has a stronger influence on cortisol release after stress in male offspring. These effects were independent of atopy status.

MeSH Terms
Adolescent Age Factors Child Female Gene Frequency Genetic Predisposition to Disease/genetics Genotype Humans Hydrocortisone/metabolism Male Mother-Child Relations Phenotype Polymorphism, Genetic/genetics Radioimmunoassay/methods Receptors, Nicotinic/genetics Saliva/metabolism Stress, Psychological/genetics,metabolism Young Adult alpha7 Nicotinic Acetylcholine Receptor
Chemicals
Chrna7 protein, human Receptors, Nicotinic alpha7 Nicotinic Acetylcholine Receptor Hydrocortisone
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sinkus Melissa L
Department of Psychiatry, University of Colorado at Denver, CO 80045, USA.
Wamboldt Marianne Z
Barton Amanda
Fingerlin Tasha E
Laudenslager Mark L
Leonard Sherry
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Article Info
Journal
Physiology & behavior
Abbr.
Physiol Behav
ISSN
1873-507X
DOI
10.1016/j.physbeh.2010.11.007
Published
2011-08-03
Epub
2010-00-10
Pages
321-6
Language
English
Region
United States
NLM ID
0151504
PMCID
PMC3094732
Subset
IM
Grants
NIMH NIH HHS · T32 MH015442 · United States
NIMH NIH HHS · MH81177 · United States
NIMH NIH HHS · R01 MH081177 · United States
NIDA NIH HHS · R01 DA009457 · United States
NIAAA NIH HHS · AA013973 · United States
NIAAA NIH HHS · R01 AA013973 · United States
NIMH NIH HHS · R01 MH081177-05 · United States
NIDA NIH HHS · DA09457 · United States
NIMH NIH HHS · T32 MH15442 · United States
NIMH NIH HHS · T32 MH015442-32 · United States
NIAAA NIH HHS · R01 AA013973-05S1 · United States
NIMH NIH HHS · R01 MH081177-04 · United States
NIDA NIH HHS · R01 DA009457-14 · United States
External Links
PubMed source DOI: 10.1016/j.physbeh.2010.11.007 PMC Full Text View journal details
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