Identification of CHRNA5 rare variants in African-American heavy smokers.
Psychiatr Genet
; 24(3): 102-9, 2014 Jun.
Article
in En
| MEDLINE
| ID: mdl-24682045
ABSTRACT
BACKGROUND:
The common CHRNA5 mis-sense coding single-nucleotide polymorphism (SNP) rs16969968G>A (D398N) has repeatedly been shown to confer risk for heavy smoking in individuals who carry the 'A' allele (encoding the 398N amino acid). The mis-sense SNP has a minor allele frequency of â¼40% in European-Americans, but only â¼7% in African-Americans (http//www.ncbi.nlm.nih.gov/projects/SNP/). We reasoned that there might be other mis-sense variants among African-Americans that could confer the heavy smoking phenotype (defined here as ≥20 cigarettes per day), perhaps in a manner similar to that of the D398N polymorphism in Europeans. MATERIALS ANDMETHODS:
As such, we resequenced 250 African-American heavy smokers, most of whom were homozygous 'G' at rs16969968G>A (minor allele frequency of 9.6% within the population).RESULTS:
Although many novel coding SNPs were not observed, we report an interesting, although rare (perhaps personal), variant in CHRNA5 that could result in nonsense-mediated decay of the aberrant transcript.CONCLUSION:
We conclude that, in African-Americans, variants (common or rare) in genes other than CHRNA5 most likely contribute toward the nicotine-dependent phenotype, either independently or in combination with variants in CHRNA5. The functional significance, on CHRNA5 expression or protein function, of the variants found here should be determined in future studies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tobacco Use Disorder
/
Black or African American
/
Receptors, Nicotinic
/
Genetic Predisposition to Disease
/
Polymorphism, Single Nucleotide
/
Nerve Tissue Proteins
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
Psychiatr Genet
Journal subject:
GENETICA
/
PSIQUIATRIA
Year:
2014
Document type:
Article
Affiliation country:
United States
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM