Sex-specific role for adenylyl cyclase type 7 in alcohol dependence.
Bottom Line: A number of downstream effectors that respond to the cAMP signals (e.g., protein kinase A, cAMP response element binding protein) have, in turn, been examined in relation to alcohol consumption.These studies did not, however, delineate the point at which the actions of alcohol on the cAMP cascade might translate into differences in drinking behavior.In the human sample, we found that single nucleotide polymorphisms in ADCY7 associate with alcohol dependence in women, and these markers are also associated with ADCY7 expression (messenger RNA) levels.
Affiliation: Medical Research Council Social, Genetic and Developmental Psychiatry, King's College London, United Kingdom. firstname.lastname@example.orgShow MeSH
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Mentions: The SNP most associated with alcohol dependence (rs2302717) is located in intron five of the ADCY7 gene and is in high LD with several markers at the 5′ region of the ADCY7 gene (Figure 2B). Notably, it completely tags rs1078151, which is located 4007 base pairs upstream of the first exon (complete LD [r2 = 1] between rs2302717 and rs1078151). The location of rs1078151 and its LD with rs2302717 suggested that the minor allele at rs2302717 (and rs1078151) might correlate with changes in ADCY7 gene expression. To test this, we analyzed whether rs2302717 correlated with ADCY7 mRNA levels in large population-based blood and adipose tissue cohorts for which genotypes and global gene expression data were available (30). These expression quantitative trait loci analyses revealed that the minor allele at rs2302717 correlated with lower ADCY7 mRNA levels in both tissues (effect estimates [SEM], p value: −.212 [.071], .0039 and −.231 [.068], .001, for adipose tissue and blood, respectively) (Figure 3). These data suggest that genotype at rs2302717 might correlate with ADCY7 mRNA expression.
Affiliation: Medical Research Council Social, Genetic and Developmental Psychiatry, King's College London, United Kingdom. email@example.com