Background and Aim: Major depressive disorder (MDD) has been ranked as the third cause of the burden of disease worldwide in 2008 by WHO, which has projected that this disease will rank first by 2030. It is diagnosed when an individual has a persistently low or depressed mood, anhedonia or decreased interest in pleasurable activities, feelings of guilt or worthlessness, lack of energy, poor concentration, appetite changes, psychomotor retardation or agitation, sleep disturbances, or suicidal thoughts. Major depression significantly affects a person\\\'s family and personal relationships, work or school life, sleeping and eating habits, and general health. A person having a major depressive episode usually exhibits a low mood, which pervades all aspects of life, and an inability to experience pleasure in previously enjoyable activities. The etiology of depression is not yet fully understood. The biopsychosocial model proposes that biological, psychological, and social factors all play a role in causing depression. Genes play a major role in the development of depression. Family and twin studies find that nearly 40% of individual differences in risk for major depressive disorder can be explained by genetic factors. Like most psychiatric disorders, major depressive disorder is likely influenced by many individual genetic changes. A number of studies have reported an association between the polymorphisms of serotonin transporter gene (SLC6A4/5-HTT) and MDD. Methods: Electronic searches were performed using PubMed. In the extensive electronic literature search, keywords “SLC6A4 gene”, “rs25531” polymorphism and “Major depression disorder”, “MDD”, “meta” were searched for prospective studies. The pooled effect sizes (ORs) along with 95% confidence intervals (CIs), in participant groups for this polymorphism. Further subgroup analyses were conducted if the data were available. Results: A meta-analysis done with STATA on 7 studies revealed that the SLC6A4 gene has a significant effect on MDD with reported pooled OR of 1.07; 95% CI = (1.13-1.01) and a p-value of 0.00 which rules out the null hypothesis which means that it has significant effect on MDD. For heterogeneity I 2 = 40.01% and H 2 = 1.67 which indicates that there is a moderate amount of heterogeneity. Conclusion: These results overall indicate strong evidence against the null hypothesis. (The null hypothesis is a typical statistical theory that suggests that no statistical relationship and significance exists in a set of given single observed variables, between two sets of observed data and measured phenomena.).

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