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A family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD)
E. Banerjee, S. Sinha, A. Chatterjee, P.K. Gangopadhyay, M. Singh,
Published in
PMID: 16583436
Volume: 141
Issue: 4
Pages: 361 - 366
Serotonin transporter (SLC6A4) polymorphisms are variously implicated in mediating susceptibility to attention-deficit-hyperactivity disorder (ADHD), a highly heritable and heterogeneous disorder with onset in childhood. Since there has been no survey in this regard from India, a sample of 56 ADHD cases and 174 healthy individuals from Kolkata were genotyped for the SLC6A4 promoter (5-HTTLPR) and intron-2 (STin2) polymorphisms. We report that the observed distribution of allele frequencies is consonant with that expected as per Hardy-Weinberg equilibrium proportions. Pair-wise combination of alleles comprising the 5-HTTLPR and STin2 polymorphic systems exhibit significant (χ2 = 14.74, df = 1; P = 0.0001) linkage disequilibrium of low magnitude (D′ = 0.269). The estimates of haplotype-based haplotype relative risk (HHRR) (χ2 = 4.92, P = 0.027; RR = 1.47; 95% CI = 1.01-2.13) and transmission disequilibrium test (TDT) statistics (χ2 = 7.00, P = 0.008; OR = 3.00; 95% CI = 1.53-5.90) using a family-based study design, indicate significant preferential transmission of the STin2.12 (A12) allele to ADHD cases. Maternal inheritance of the A12 allele is significant in terms of the HHRR (χ2 = 6.53, P = 0.011; RR = 2.00; 95% CI = 1.08-3.72) and TDT (χ2 = 8.07, P = 0.005; OR = 6.50; 95% CI = 1.76-23.98) suggesting a novel role for epigenetic mechanisms in the etiology of ADHD. Similar analyses yielded no evidence of association between the 5-HTTLPR polymorphism and ADHD. Studies including additional polymorphic markers, ADHD subjects and other ethnic groups are warranted to further substantiate the present findings. © 2006 Wiley-Liss, Inc.
About the journal
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics