DRD2 and DRD4 genes related to cognitive deficits in HIV-infected adults who abuse alcohol

Karina Villalba, Jessy G. Devieux, Rhonda Rosenberg, Jean Lud Cadet

HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. The causes of neurocognitive impairment are still unclear. However, several factors have been suggested including the role of genetics. There is evidence suggesting that neurocognitive impairment is heritable and individual differences in cognition are strongly driven by genetic variations. The contribution of genetic variants affecting the metabolism and activity of dopamine may influence these individual differences. The present study explored the relationship between two candidate genes (DRD4 and DRD2) and neurocognitive performance in HIV-infected adults. A total of 267 HIV-infected adults were genotyped for polymorphisms, DRD4 48 bp-variable number tandem repeat (VNTR), DRD2 rs6277 and ANKK1 rs1800497. The Short Category (SCT), Color Trail (CTT) and Rey-Osterrieth Complex Figure Tests (ROCT) were used to measure executive function and memory. Results showed significant associations with the SNP rs6277 and impaired executive function (odds ratio = 3.3, 95 % CI 1.2-2.6; p = 0.004) and cognitive flexibility (odds ratio = 1.6, 95 % CI 2.0-5.7; p = 0.001). The results were further stratified by race and sex and significant results were seen in males (odds ratio = 3.5, 95 % CI 1.5-5.5; p = 0.008) and in African Americans (odds ratio = 3.1, 95 % CI 2.3-3.5; p = 0.01). Also, DRD4 VNTR 7-allele was significantly associated with executive dysfunction. The study shows that genetically determined differences in the SNP rs6277 DRD2 gene and DRD4 48 bp VNTR may be risk factors for deficits in executive function and cognitive flexibility.