Evidence of association of serotonin transporter gene polymorphisms with schizophrenia in a South Indian population.
Serotonin (5-hydroxytryptamine (5-HT)) transporter (SLC6A4) is known to influence mood, emotion, cognition and efficacy of antidepressants, particularly that of selective serotonin reuptake inhibitors. Atypical antipsychotics exert their effects partially through serotinergic systems, and hence, variation in 5-HT uptake may affect antipsychotic action mediated through the serotinergic system. Therefore, investigating the role of SLC6A4 as a risk factor for developing schizophrenia and treatment response had been a point of concern for many investigators, but with variable outcome. In this study, we examined the genetic roles of five polymorphisms of SLC6A4, including those of the widely studied 44 base pair variable number of tandem repeat (VNTR) in the promoter region of SLC6A4 (the serotonin transporter gene-linked polymorphic region: 5HTTLPR) and a VNTR polymorphism (STin2) in the second intron, in schizophrenia and its influence on the severity of symptoms in a South Indian population from Kerala, comprising 586 individuals. We detected significant allelic and genotypic associations with rs2066713 (both allelic and genotypic P-value <0.001), 5HTTLPR (allelic P-value=0.008 and genotypic P-value=0.03) and STin2 polymorphisms (allelic P-value=0.001 and genotypic P-value=0.002). A haplotype linking these three risk alleles, 5HTTLPR/S-rs2066713/C-STin2/12-repeat (P-value=0.0059), was also significantly associated with disease in our population. Patients with STin2 12-repeat homozygotes showed a greater severity of blunted effect symptom. These results suggest a strong role of SLC6A4 in schizophrenia, possibly with a specific behavioral endophenotype in a South Indian population.
Vijayan
Neetha N
NN
Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
Iwayama
Yoshimi
Y
Koshy
Linda V
LV
Natarajan
Chandrasekhar
C
Nair
Chandrashekharan
C
Allencherry
Priya M
PM
Yoshikawa
Takeo
T
Banerjee
Moinak
M
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins