Analysis of polymorphisms in the dopamine beta hydroxylase gene: association with attention deficit hyperactivity disorder in Indian children

Abstract

Objective: To study the association of Attention Deficit Hyperactivity Disorder (ADHD) and polymorphism in the dopamine beta hydroxylase (DBH) gene in Indian ADHD cases.

Subjects: Forty one ADHD cases were diagnosed as per the DSM-IV-TR criteria and evaluated by Conners Parents and Teachers Rating Scale and Wechslers Intelligence Scale for Children.

Methods: Genomic DNA was amplified for exon 2 *444g/a and intron 5 (Taq I) polymorphism in the DBH gene followed by restriction fragment length polymorphism (RFLP) analysis. Haplotype-based haplotype relative risk (HHRR) was analyzed to ascertain the transmission pattern of these two polymorphisms in ADHD cases. Linkage disequilibrium (LD) between the two polymorphisms was calculated using EH+ and 2LD programs.

Results: In the limited number of samples analyzed, a slight increase in transmission of the 444a allele in ADHD subjects was observed for DBH 444g/a. The intron 5 (Taq I) polymorphism showed no significant association with ADHD in these cases. Strong disequilibrium was observed between DBH444g/a and intron 5 (Taq I) polymorphism.

Conclusion: This is the first molecular genetic study on ADHD in Indian subjects exploring transmission of polymorphisms in the DBH gene. Preliminary investigation shows a trend towards association between the transmission of DBH444a allele and ADHD. No association was noticed between transmission of intron 5 (Taq I) polymorphism and ADHD in the Indian subjects. Presence of strong LD may point towards co-segregation of these two polymorphisms more often than expected.