Sex differences in TTC12/ANKK1 haplotype associations with daily tobacco smoking in Black and White Americans.
BACKGROUND
The 11q23.1 genomic region has been associated with nicotine dependence in Black and White Americans.


METHODS
By conducting linkage disequilibrium analyses of 7 informative single nucleotide polymorphisms (SNPs) within the tetratricopeptide repeat domain 12 (TTC12)/ankyrin repeat and kinase containing 1 (ANKK1)/dopamine (D2) receptor gene cluster, we identified haplotype block structures in 270 Black and 368 White (n = 638) participants, from the Baltimore Epidemiologic Catchment Area cohort study, spanning the TTC12 and ANKK1 genes consisting of three SNPs (rs2303380-rs4938015-rs11604671). Informative haplotypes were examined for sex-specific associations with daily tobacco smoking initiation and cessation using longitudinal data from 1993-1994 and 2004-2005 interviews.


RESULTS
There was a Haplotype x Sex interaction such that Black men possessing the GTG haplotype who were smokers in 1993-2004 were more likely to have stopped smoking by 2004-2005 (55.6% GTG vs. 22.0% other haplotypes), while Black women were less likely to have quit smoking if they possessed the GTG (20.8%) versus other haplotypes (24.0%; p = .028). In Whites, the GTG haplotype (vs. other haplotypes) was associated with lifetime history of daily smoking (smoking initiation; odds ratio = 1.6; 95% CI = 1.1-2.4; p = .013). Moreover, there was a Haplotype x Sex interaction such that there was higher prevalence of smoking initiation with GTG (77.6%) versus other haplotypes (57.0%; p = .043).


CONCLUSIONS
In 2 different ethnic American populations, we observed man-woman variation in the influence of the rs2303380-rs4938015-rs11604671 GTG haplotype on smoking initiation and cessation. These results should be replicated in larger cohorts to establish the relationship among the rs2303380-rs4938015-rs11604671 haplotype block, sex, and smoking behavior.
Division of Family & Community Medicine, Department of Medicine, Center for Education in Family & Community Medicine, Stanford University School of Medicine, 1215 Welch Road, Modular G, Stanford, CA 94305-5408, USA. spdavid@stanford.edu
Sean P
SP
David
Briana
B
Mezuk
Peter P
PP
Zandi
David
D
Strong
James C
JC
Anthony
Raymond
R
Niaura
George R
GR
Uhl
William W
WW
Eaton
D001741:Black or African American / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012727:Sex Characteristics; D012907:Smoking / Q000235:genetics*; D044465:White People / Q000235:genetics*
D011506:Proteins; C487552:TTC12 protein, human; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases