Serotonin transporter gene, depressive symptoms, and interleukin-6.
BACKGROUND
We explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels.


RESULTS
We genotyped 20 polymorphisms in 360 male twins (mean age, 54 years) from the Vietnam Era Twin Registry. Current depressive symptoms were measured with the Beck Depression Inventory II. IL-6 was assessed using a commercially available ELISA kit. Genotype associations were analyzed using generalized estimating equations. To study how SLC6A4 genetic vulnerability influences the relationship between depressive symptoms and IL-6, bivariate models were constructed using structural equation modeling. Of the 20 polymorphisms examined, the effective number of independent tests was 6, and the threshold of significance after Bonferroni correction was 0.008. There were 6 single-nucleotide polymorphisms significantly associated with Beck Depression Inventory (P< or =0.008), including rs8071667, rs2020936, rs25528, rs6354, rs11080122, and rs8076005, and 1 single-nucleotide polymorphism was borderline associated (rs12150214, P=0.017). Of these 7 single-nucleotide polymorphisms, 3 were also significantly associated with IL-6 (P<0.008), including rs25528, rs6354, and rs8076005, and the other 4 were borderline associated (P=0.009 to 0.025). The subjects with 1 copy of the minor allele of these 7 single-nucleotide polymorphisms had higher Beck Depression Inventory scores and IL-6 levels. Further bivariate modeling revealed that approximately 10% of the correlation between Beck Depression Inventory and IL-6 could be explained by the SLC6A4 gene.


CONCLUSIONS
Genetic vulnerability involving the SLC6A4 gene is significantly associated with both increased depressive symptoms and elevated IL-6 plasma levels. Common pathophysiological processes may link depression and inflammation, and implicate the serotonin pathway in neural-immune interactions.
Su
Shaoyong
S
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Zhao
Jinying
J
Bremner
J Douglas
JD
Miller
Andrew H
AH
Tang
Weining
W
Bouzyk
Mark
M
Snieder
Harold
H
Novik
Olga
O
Afzal
Nadeem
N
Goldberg
Jack
J
Vaccarino
Viola
V
D003863:Depression / Q000097:blood* / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014427:Twins / Q000235:genetics
D015850:Interleukin-6; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins