Association between CANCA1C gene rs1034936 polymorphism and alcohol dependence in bipolar disorder

Bipolar disorder (BD) is a highly heritable and disabling mental illness, commonly associated with substance abuse, being alcohol abuse the most frequent. Comorbid BD and substance abuse disorders are often associated with high levels of health service utilization and destabilization of the course of illness resulting in poor treatment outcomes. Although recent genome-wide association studies have detected a number of risk genes for BD, the data is still sparse and inconclusive for those genes that may contribute to the increased risk of comorbid alcohol abuse (AA) in BD. The primary aim of the present study was to investigate the effects of 46 single-nucleotide polymorphisms (SNPs) within eight genes on different phenotypes of BD patients, such as comorbid alcohol abuse. We further assessed clinical variables associated with AA.

One-hundred fifty-eight BD I and II patients were enrolled in a naturalistic cohort study. Genomic DNA of 92 patients was extracted from whole blood using standard procedures and 46 tag SNPs in eight genes of interest (ANK, CACNA1C, CACNB2, FKBP5, GRM7, ITIH3, SYNE1 and TCF4) were genotyped.

Seventy-one patients out of 158 (45%) satisfied diagnostic criteria for comorbid AA. Among 46 SNPs analyzed, the only SNP associated with comorbid AA was rs1034936 polymorphism in the CANCA1C gene. This polymorphism was also associated with lifetime cocaine abuse, manic switch and current atypical antipsychotics.

Our findings suggest a role of rs1034936 CACNA1C gene variant in BD-AA group. Despite their preliminary nature, the present results may provide new insight on mechanisms underlying AA in BD.