Case-control study reveals combined 5-HTTLPR and GNbeta3 polymorphisms significantly elevate risk of depressive disorder, suggesting an interactive genetic vulnerability.
OBJECTIVE: To assess whether the promoter region of the serotonin transporter gene (5-HTTLPR) and G-protein beta3-subunit (GNbeta3 C825T) polymorphisms are associated with depressive disorder and explore the genetic mechanism concerning the pathogenesis of this disorder. METHODS: The genotypes were determined with polymerase chain reaction and allele-specific restriction enzyme analysis. Patients suffering from depression (n=184) and sex and age-matched controls (n=158) were compared in this study. RESULTS: The frequencies of 5-HTTLPR SS and GNbeta3 825TT genotypes and 5-HTTLPR S and GNbeta3 825T alleles in patients suffering from depression were significantly higher than those in the controls (P<0.01). Combined genotype analysis showed that individuals with both 5-HTTLPR S and GNbeta3 825T alleles (odds ratio=3.25, P=0.002) had a risk of depressive disorder higher than those with 5-HTTLPR S (odds ratio=1.817, P=0.01) or GNbeta3 825T alleles (odds ratio=2.214, P=0.001) alone. CONCLUSIONS: These results indicated that the etiology of depressive disorder is associated with 5-HTTLPR and GNbeta3 C825T polymorphisms. Our data also suggests that an interaction effect may exist between the 5-HTTLPR S allele and GNbeta3 825T allele in increasing the risk of depressive disorder.
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Cao et al. (2007) studied this question.
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