Neuronal calcium sensor-1 and cocaine addiction: A genetic association study in African-Americans and European Americans |
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Authors: | Pushpinder K. Multani,Toni-Kim Clarke,Sneha Narasimhan,Lisa Ambrose-Lanci,Kyle M. Kampman,Helen M. Pettinati,David W. Oslin,Charles P. O&rsquo Brien,Wade H. Berrettini,Falk W. Lohoff |
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Affiliation: | 1. Psychiatric Pharmacogenetics Laboratory, Center for Neurobiology and Behavior, Department of Psychiatry, Philadelphia, PA, USA;2. Treatment Research Center, University of Pennsylvania School of Medicine, Philadelphia, PA, USA |
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Abstract: | Genes involved in drug reward pathways are plausible candidates for susceptibility to substance use disorders. Given the prominent role of dopamine in drug reward, dopamine receptor-interacting proteins (DRIPs) such as the neuronal calcium sensor-1 (NCS-1) protein have been hypothesized to play a role in the pathophysiology of cocaine addiction (CA). In this study, we investigated whether genetic variants in the NCS-1 gene confer risk to CA. We genotyped 8 SNPs (rs4837479, rs7849345, rs3824544, rs10819611, rs947513, rs2277200, rs7873936 and rs1342043) in our discovery sample (cases n = 796, controls n = 416) of African descent. Confirmation of associated or trending SNPs (rs7849345, rs10819611, rs1342043) was attempted using a replication sample of African American (AA) ethnicity (cases n = 335, controls n = 336) and European-American (EA) ancestry (cases n = 336, controls n = 656). Secondary sex specific analysis was also carried out for each SNP in both AA and EA individuals. Genotyping of the discovery cohort showed significant genotypic (p = 0.0005, corrected q-value) as well as allelic (p = 0.005, corrected q-value) associations of rs1342043 with CA in AAs; however, this marker could not be confirmed in either the AA or EA replication sample. Combined analysis of all AA samples (n = 1883) for rs1342043 showed a significant association with CA (genotypic p = 0.0001, allelic p = 0.002) with a gender specific effect for males (allelic p = 0.005, genotypic p = 0.0003). Our data suggest that genetic variants in the NCS-1 gene contribute to susceptibility of CA in individuals of African descent. |
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Keywords: | Addiction Cocaine NCS-1 African Americans European Americans |
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