SLC1A3 C3590T but not BDNF G196A is a predisposition factor for stress as well as depression, in an adolescent eastern Indian population

Abstract

Background: Adolescence is a distinctive stage of various changes and is noted as peak age for onset of many psychiatric disorders, especially linked to stress and depression. Several genetic variations are being increasingly known to be linked with stress and depression. The polymorphisms in two such genes, the BDNF and SLC1A3, have been reported to be linked with either depression/stress or with suicidal behaviour. These genes have not been validated in Indian population, and therefore there is a need to investigate these genes in Indian population. The present study was undertaken to test whether the known polymorphisms SLC1A3 C3590T, SLC1A3 C869G and BDNF G196A are associated or not with stress or depression in an eastern Indian population.

Methods: A case-control association study was performed with 108 cases having variable levels of stress and depression and 205 matched controls. Detection of stress and depression was done by using standard instruments as PSS and CES-D, respectively and demographic profile was obtained for each individual on the basis of personal data sheet. Genotyping for the selected polymorphisms was performed by PCR followed by restriction digestion.

Results: The SNP SLC1A3 C3590T was found to be associated with stress and depression (p = 0.0042, OR = 2.072). Therefore, the T allele increases the risk by more than two folds for stress and depression in the present population. The other allele of SLC1A3, G869C, as well as BDNF G196A were not associated with stress or depression in the population studied.

Conclusion: SLC1A3 C3590T is a predisposition factor for stress and depression in an eastern Indian population, whereas SLC1A3 G869C and BDNF G196A were not found to be a risk factor. Therefore, presence of T allele of SLC1A3 C3590T, may predict the development of stress and depression in an individual. This may also help in the understanding of pathophysiology of the disease. However, these findings warrant a wider study in Indian populations and would be of significance in understanding the predisposition of stress and depression in this population.

Keywords: Adolescent; BDNF; Depression; India; Polymorphism; SLC1A3; Stress.

Fig. 1

Restriction digestion by PflF1 of SLC1A3 C3590T amplicon of representative individuals. The amplicon of SLC1A3 C3590T after digestion with the restriction endonuclese, PflF1, in normal condition (i.e when C is present at 3590 position) shows two fragments of DNA, 157 and 75 bp (lane 1, 3, 4, 6, 7, 10). A substitution of T in place of C, causes loss of restriction site and only one band of 232 bp (full sized amplicon; lane 5) is obtained. Heterozygotes on the other hand shows three bands of 232, 157 and 75 bp (lane 2, 8, 9, 11, 12)

Fig. 2

Restriction digestion by BstU1 of SLC1A3 C869G amplicon of representative individuals. This polymorphism was not found in the cohort of individuals selected and a full length amplicon of 223 bp, is seen in all the lanes. The cases and controls with reference to stress and depression showed no heterozygotes in control as well cases

Fig. 3

Restriction digestion of BDNF G196A amplicon by NlaIII of representative individuals. The amplicon after digestion in normal condition (i.e. in presence of major allele G) N = major allele (homozygotes) which gives two bands of 216 and 58 bp (Lane 1, 3, 7, 9, 10); A substitution of A in place of G creates new restriction site, so Mut = minor allele (homozygotes) giving three bands of 139, 77 and 58 bp (lane 2) and Heterozygotes having both types of alleles forms 4 bands Het = heterozygotes, which give four bands of 216, 139, 77 and 58 bp (lane 4, 5, 6)