Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2005-02, Vol.133B (1), p.93-96
• Main Authors: Mulder, Erik J., Anderson, George M., Kema, Ido P., Brugman, Astrid M., Ketelaars, Cees E.J., de Bildt, Annelies, van Lang, Natasja D.J., den Boer, Johan A., Minderaa, Ruud B.
• Format: Article
• Language: English
• Subjects: 5-HTTLPR; Adolescent; Adult; Alleles; autistic disorder; Autistic Disorder - complications; Autistic Disorder - genetics; Child; Child Development Disorders, Pervasive - complications; Child Development Disorders, Pervasive - genetics; Child, Preschool; Compulsive Behavior - complications; Compulsive Behavior - genetics; Female; Gene Frequency; Genotype; Haplotypes; HTT(SLC6A4); Humans; intron 2 VNTR; Introns - genetics; Linkage Disequilibrium; Male; Membrane Glycoproteins - genetics; Membrane Transport Proteins - genetics; Minisatellite Repeats - genetics; Multivariate Analysis; Nerve Tissue Proteins - genetics; Netherlands; Polymorphism, Genetic; Promoter Regions, Genetic - genetics; Risk Factors; Serotonin Plasma Membrane Transport Proteins; serotonin transporter gene
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30122

Two putatively functional polymorphisms of the serotonin transporter gene (HTT, SLC6A4) were examined for associations with risk for pervasive developmental disorders (PDDs) and specific autism phenotypes. Dutch patients diagnosed with PDD (N = 125, age range 5–20 years, DSM‐IV‐TR based criteria, ADI‐R and ADOS behavioral assessments) and their parents (N = 230) were genotyped for promoter ins/del (5‐HTTLPR) and intron 2 variable number of tandem repeats (VNTR) alleles. Using the transmission disequilibrium test (TDT), no disorder‐specific preferential transmission of promoter (long and short) or intron 2 (10‐ and 12‐repeat) alleles was observed. However, multivariate analysis of continuous autism‐related behavioral measures revealed that subjects with intron 2 12/12 genotype were significantly more impaired in the rigid‐compulsive domain (P = 0.008). Quantitative TDT (QTDT) analysis also showed significant association of the intron 2 VNTR 12‐repeat allele with rigid‐compulsive behavior (P = 0.015). These results suggest that intron 2 VNTR alleles or nearby polymorphisms in linkage disequilibrium may play a role in specific aspects of the behavioral phenotype of autism. © 2004 Wiley‐Liss, Inc.