Intronic variants in the dopa decarboxylase (DDC) gene are associated with smoking behavior in European-Americans and African-Americans.
We report here a study considering association of alleles and haplotypes at the DOPA decarboxylase (DDC) locus with the DSM-IV diagnosis of nicotine dependence (ND) or a quantitative measure for ND using the Fagerstrom Test for Nicotine Dependence (FTND). We genotyped 18 single nucleotide polymorphisms (SNPs) spanning a region of approximately 210 kb that includes DDC and the genes immediately flanking DDC in 1,590 individuals from 621 families of African-American (AA) or European-American (EA) ancestry. Evidence of association (family-based tests) was observed with several SNPs for both traits (0.0002<or=P<or=0.04). The most significant result was obtained for the relationship of FTND score to SNP rs12718541 (AA families: P=0.002; EA families: P=0.03; all families: P=0.0002) which is in the same intron as the splice site for a neuronal isoform of human DDC lacking exons 10-15. Haplotype analysis did not reveal any SNP combination with stronger evidence for association than rs12718541 alone. Although sequence analysis suggests that rs12718541 may be an intronic splicing enhancer, further studies are needed to determine whether a direct link exists between an alternatively spliced form of DDC and predisposition to ND. These findings confirm a previous report of association of DDC with ND, localize the causative variants to the 3' end of the coding region and extend the association to multiple population groups.
Yu
Yi
Y
Department of Medicine, Genetics Program, Boston University School of Medicine, MA, USA.
Panhuysen
Carolien
C
Kranzler
Henry R
HR
Hesselbrock
Victor
V
Rounsaville
Bruce
B
Weiss
Roger
R
Brady
Kathleen
K
Farrer
Lindsay A
LA
Gelernter
Joel
J
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D004296:Dopa Decarboxylase / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014029:Tobacco Use Disorder / Q000201:enzymology* / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics
D004296:Dopa Decarboxylase