Serotonin transporter (5-HTT) gene polymorphisms and susceptibility to cocaine dependence among African-American individuals.
Studies indicate that the serotonin system, particularly the serotonin transporter (5-HTT), may modulate the central effects of cocaine. We investigated whether a polymorphism in the 5' promotor region (5-HTTLPR) of the 5-HTT gene confers susceptibility to cocaine dependence. One hundred and ninety-seven cocaine-dependent African-American subjects and 101 controls were studied. Polymerase chain reaction based genotyping of a biallelic repeat polymorphism in the 5' promotor region yielded 2 alleles containing 484 (S) and 528 bp (L) repeats, respectively. There were no significant differences between controls of European background (n = 40) and African-American controls (n = 61) in distribution of genotypes (European: LL = 32.5%, LS = 40.0%, SS = 27.5%; African-American: LL = 27.9%, LS = 57.4%, SS = 14.7%) (chi(2) = 3.60, df = 2, p = 0.16) or allele frequencies (European: L = 52.5%, S = 47.5%; African-American: L = 56.6%, S = 43.4%) (chi(2) = 2.21, df = 1, p = 0.13). When cocaine patients were compared to an ethnically diverse control group (n = 101), frequencies of the L variant (65.0%) were significantly higher while the S variant (35.0%) was less frequent among cocaine patients compared to controls (L = 53.9%, S = 46.1%) (chi(2) = 6.83, df = 1, p < 0.01). Similarly, there were more cocaine patients with the LL genotype (41.1%) and less with the SS genotype (11.2%) compared to controls (LL = 29.7%, SS = 21.8%) (chi(2) = 7.43, df = 2, p < 0.05). However, after restricting controls to African-American individuals only (n = 61), cocaine subjects and controls did not differ significantly with respect to genotype distribution (chi(2) = 4.24, df = 2, p = 0.12) or allele frequencies (chi(2) = 2.83, df = 1, p = 0.10). In conclusion, although comparisons with a heterogeneous control group indicated a possible association between allelic variants of 5-HTTLPR and cocaine dependence among African-American cocaine subjects, this relationship was not observed when the control group was limited to African-American people only. Our findings need to be confirmed on larger samples of ethnically matched individuals.
Patkar
Ashwin A.
AA
Division of Substance Abuse Programs, Department of Psychiatry and Human Behavior, Thomas Jefferson University, Philadelphia, PA, USA.
Berrettini
Wade H.
WH
Hoehe
Margaret
M
Hill
Kevin P.
KP
Sterling
Robert C.
RC
Gottheil
Edward
E
Weinstein
Stephen P.
SP