Published Online
on October 9, 2009

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Original Article

Serotonin Transporter Gene, Depressive Symptoms and Interleukin-6

Shaoyong Su¹; Jinying Zhao¹; J.Douglas Bremner¹; Andrew H. Miller¹; Weining Tang¹; Mark Bouzyk¹; Harold Snieder²; Olga Novik³; Nadeem Afzal¹; Jack Goldberg⁴ and Viola Vaccarino^1,5

¹ Emory University School of Medicine, Atlanta, GA;
² Univ Med Ctr Groningen, Univ of Groningen, The Netherlands & King's Colg, London, United Kingdom;
³ Tufts Medical Center, Boston, MA;
⁴ University of Washington, Seattle, WA

^* Corresponding author; email: viola.vaccarino{at}emory.edu

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.

Methods and Results—We genotyped 20 polymorphisms in 360 male twins (mean age: 54) from the Vietnam Era Twin Registry. Current depressive symptoms were measured with the Beck Depression Inventory-II (BDI-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 SNPs significantly associated with BDI (P0.008), including rs8071667, rs2020936, rs25528, rs6354, rs11080122 and rs8076005, and 1 SNP borderline associated (rs12150214, P=0.017). Of these 7 SNPs, 3 were also significantly associated with IL-6 (P<0.008), including rs25528, rs6354 and rs8076005, and the other 4 were borderline associated (P=0.009~0.025). The subjects with one copy of the minor allele of these 7 SNPs had higher BDI scores and IL-6 levels. Further bivariate modeling revealed that approximately 10% of the correlation between BDI 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.

Key Words: atherosclerosis • epidemiology • genetics • inflammation • depression