Association of serotonin and GABA pathway gene polymorphisms with alcohol dependence: A preliminary study

Alcohol dependence (AD), characterized by profound disruptions in specific circuits of the brain is influenced by both environmental, which play a significant role in developing addiction and genetic factors, which make some individuals more susceptible to disruptions. Various polymorphisms in the neurotransmitter genes are reported to increase the risk of developing dependence. The present study aimed to identify association of serotonin and GABA polymorphisms with AD in Indian subjects.

The study group comprised of 141 AD cases recruited as per DSM IV TR criteria from the outpatient Department of Psychiatry and 110 volunteers from the general population. Clinical and family history was noted and 5 ml blood drawn for genetic studies. Polymorphisms 5-HTTLPR and STin2 of serotonin and rs2279020 and rs3219151 of the GABA pathway were analyzed and results correlated with age at first use quantity consumed, duration of use, dependence and age at onset of dependence.

The marker frequencies were similar between cases and controls except for rs3219151. 5-HTTLPR was significantly associated with high AUDIT scores and alcohol intake (p < 0.0001), GABA_A rs2279020 and rs3219151 with age at first use (p < 0.0001); rs2279020 with higher AUDIT score (p = 0.002) and rs3219151 with quantity (p = 0.0001). High frequency of GABRA6 rs3219151 TT genotype in AD and its association with lower age at first use, higher intake/day, and higher duration of dependence appears to confer risk.

This preliminary study, though on a smaller sample size, suggests an association of 5-HTTLPR and GABA_A receptor polymorphisms with AD in our population.