The International Journal of Neuropsychopharmacology

Brief Report

Obsessive–compulsive disorder and the promoter region polymorphism (5-HTTLPR) in the serotonin transporter gene (SLC6A4): a negative association study in the Afrikaner population

Craig J. Kinnear a1, Dana J. H. Niehaus a2, Johanna C. Moolman-Smook a1, Pieter L. du Toit a2, Jeanine van Kradenberg a2, Jakobus B. Weyers a1, Annemarie Potgieter a2, Vanessa Marais a2, Robin A. Emsley a2, James A. Knowles a3, Valerie A. Corfield a1, Paul A. Brink a1 and Dan J. Stein a2c1
a1 MRC/US Centre for Molecular and Cellular Biology, University of Stellenbosch, PO Box 19063, Tygerberg 7505
a2 MRC Unit on Anxiety and Stress Disorders, University of Stellenbosch, PO Box 19063, Tygerberg 7505
a3 Columbia Genome Centre, Columbia University and the New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032


A polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) has been reported to have functional significance and to be associated with obsessive–compulsive disorder (OCD). However, other studies have generated confounding results. A study was undertaken to re-evaluate this association in subjects drawn from the relatively genetically homogeneous Afrikaner population of South Africa. Fifty-four OCD patients of Afrikaner descent and 82 ethnically matched control individuals were phenotyped and genotyped. No significant association was found between the distribution of the 5-HTTLPR genotypes at the SLC6A4 locus and OCD. A similar result (p = 0.108) was generated when a meta-analysis of the 5-HTTLPR polymorphism, combining the current study with a previously reported Caucasian group, was performed; the meta-study comprised 129 OCD patients and 479 control individuals. However, both studies lacked power. Therefore, evidence that variation in SLC6A4 plays a significant role in the development of OCD in the population groups studied is inconclusive. Future association studies in Caucasian populations may extend the power of such meta-analyses and assist in delineating the role of SLC6A4 in OCD.

(Received January 25 2000)
(Reviewed April 3 2000)
(Revised June 21 2000)
(Accepted June 29 2000)

Key Words: Serotonin; serotonin transporter; polymorphism; Afrikaner.

c1 Address for correspondence: Professor D. J. Stein, MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Medical School, PO Box 19063, Tygerberg 7505, South Africa. Tel.: +27219389161 Fax: +27219335790 E-mail: