Investigation of DUSP8 and CALCA in alcohol dependence.

Evidence for genetic linkage to alcohol dependence was found on chromosome 11p15.5 from an autosome-wide scan in a Southwestern Native American population. The purpose of this study was to identify genes that may underlie this linkage signal. Two genes, calcitonin/calcitonin-related polypeptide alpha (CALCA) and dual specificity phosphatase 8 (DUSP8), met our criteria for candidacy, and were sequenced to identify polymorphisms that may be relevant to disease. Both genes play a role in various pathways known to underlie the pathophysiological mechanisms leading to development of alcohol dependence. While no polymorphisms were found in CALCA, four novel polymorphisms were found in DUSP8, one of which led to an amino acid substitution. Genotyping of this functional variant in 463 Southwestern Native Americans revealed no significant association between the DUSP8 C712T (Ala193Val) polymorphism and alcohol dependence (odds ratio = 1.48 95% CI 0.6-3.92).