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Study of the association of serotonin transporter triallelic 5-HTTLPR and STin2 VNTR polymorphisms with lithium prophylaxis response in bipolar disorder

Tharoor, Hemaa,c*; Kotambail, Ananthapadmanabhab*; Jain, Sanjeevd; Sharma, Podila Satya Venkata Narasimhac; Satyamoorthy, Kapaettub

doi: 10.1097/YPG.0b013e32835d6fad
Brief Reports

The 5-hydroxy tryptamine transporter (5-HTT) gene has been previously implicated in lithium response, but the roles of the triallelic 5-HTT linked promoter region (5-HTTLPR) and variable number tandem repeats in the second intron [serotonin transporter intron 2 (STin2)] have not been reported. We examined these polymorphisms in 122 patients with bipolar I disorder, among which 49 patients were classified as good responders, 49 as nonresponders, and 24 as partial responders to lithium prophylaxis. We observed significant variation in the genotype frequencies of STin2 polymorphism among the response groups (P=0.02). There was also a significant association of haplotype consisting of the S allele of 5-HTTLPR and 10 repeat allele of STin2 with lithium response (P=0.01) and no such relationship was found with 5-HTTLPR variants. Our data support preliminary information of a possible association of STin2 and its combined effect with 5-HTTLPR variants with lithium response and also suggest that lithium is likely to be more effective for patients carrying 5-HTT polymorphisms associated with reduced transcriptional activity.

aSchizophrenia Research Foundation, Chennai

bDivision of Biotechnology, Manipal Life Sciences Centre

cDepartment of Psychiatry, Kasturba Medical College, Manipal University, Manipal

dDepartment of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India

*Hema Tharoor and Ananthapadmanabha Kotambail contributed equally to the writing of this article.

Correspondence to Hema Tharoor, DPM, DNB, MNAMS, Schizophrenia Research Foundation, R-7A North Main Road, Anna Nagar West (Extn.), Chennai 600 101, Tamil Nadu, India Tel: +91 44 261 539 71; fax: +91 44 261 539 71; e-mail:

Received January 19, 2011

Accepted August 1, 2012

© 2013 Lippincott Williams & Wilkins, Inc.