Serotonin transporter gene, depressive symptoms,and interleukin-6

Shaoyong Su, Jinying Zhao, J. Douglas Bremner, H. Miller Andrew, Mark Bouzyk, Harold Snieder, Olga Novik, Nadeem Afzal, Goldberg Jack Goldberg, Viola Vaccarino

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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 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≤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 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.

Original languageEnglish (US)
Pages (from-to)614-620
Number of pages7
JournalCirculation: Cardiovascular Genetics
Volume2
Issue number6
DOIs
StatePublished - Dec 1 2009

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Interleukin-6
Depression
Genes
Single Nucleotide Polymorphism
Equipment and Supplies
Neural Pathways
Vietnam
Synaptic Transmission
Registries
Serotonin
Enzyme-Linked Immunosorbent Assay
Alleles
Genotype
Inflammation

Keywords

  • Atherosclerosis
  • Depression
  • Epidemiology
  • Genetics
  • Inflammation

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Su, S., Zhao, J., Bremner, J. D., Andrew, H. M., Bouzyk, M., Snieder, H., ... Vaccarino, V. (2009). Serotonin transporter gene, depressive symptoms,and interleukin-6. Circulation: Cardiovascular Genetics, 2(6), 614-620. https://doi.org/10.1161/CIRCGENETICS.109.870386

Serotonin transporter gene, depressive symptoms,and interleukin-6. / Su, Shaoyong; Zhao, Jinying; Bremner, J. Douglas; Andrew, H. Miller; Bouzyk, Mark; Snieder, Harold; Novik, Olga; Afzal, Nadeem; Jack Goldberg, Goldberg; Vaccarino, Viola.

In: Circulation: Cardiovascular Genetics, Vol. 2, No. 6, 01.12.2009, p. 614-620.

Research output: Contribution to journalArticle

Su, S, Zhao, J, Bremner, JD, Andrew, HM, Bouzyk, M, Snieder, H, Novik, O, Afzal, N, Jack Goldberg, G & Vaccarino, V 2009, 'Serotonin transporter gene, depressive symptoms,and interleukin-6', Circulation: Cardiovascular Genetics, vol. 2, no. 6, pp. 614-620. https://doi.org/10.1161/CIRCGENETICS.109.870386
Su, Shaoyong ; Zhao, Jinying ; Bremner, J. Douglas ; Andrew, H. Miller ; Bouzyk, Mark ; Snieder, Harold ; Novik, Olga ; Afzal, Nadeem ; Jack Goldberg, Goldberg ; Vaccarino, Viola. / Serotonin transporter gene, depressive symptoms,and interleukin-6. In: Circulation: Cardiovascular Genetics. 2009 ; Vol. 2, No. 6. pp. 614-620.
@article{fce0f35dd479482598afcbb354840231,
title = "Serotonin transporter gene, depressive symptoms,and interleukin-6",
abstract = "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 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≤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 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.",
keywords = "Atherosclerosis, Depression, Epidemiology, Genetics, Inflammation",
author = "Shaoyong Su and Jinying Zhao and Bremner, {J. Douglas} and Andrew, {H. Miller} and Mark Bouzyk and Harold Snieder and Olga Novik and Nadeem Afzal and {Jack Goldberg}, Goldberg and Viola Vaccarino",
year = "2009",
month = "12",
day = "1",
doi = "10.1161/CIRCGENETICS.109.870386",
language = "English (US)",
volume = "2",
pages = "614--620",
journal = "Circulation. Genomic and precision medicine",
issn = "1942-325X",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "6",

}

TY - JOUR

T1 - Serotonin transporter gene, depressive symptoms,and interleukin-6

AU - Su, Shaoyong

AU - Zhao, Jinying

AU - Bremner, J. Douglas

AU - Andrew, H. Miller

AU - Bouzyk, Mark

AU - Snieder, Harold

AU - Novik, Olga

AU - Afzal, Nadeem

AU - Jack Goldberg, Goldberg

AU - Vaccarino, Viola

PY - 2009/12/1

Y1 - 2009/12/1

N2 - 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 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≤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 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.

AB - 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 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≤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 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.

KW - Atherosclerosis

KW - Depression

KW - Epidemiology

KW - Genetics

KW - Inflammation

UR - http://www.scopus.com/inward/record.url?scp=77449119049&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77449119049&partnerID=8YFLogxK

U2 - 10.1161/CIRCGENETICS.109.870386

DO - 10.1161/CIRCGENETICS.109.870386

M3 - Article

C2 - 20031642

AN - SCOPUS:77449119049

VL - 2

SP - 614

EP - 620

JO - Circulation. Genomic and precision medicine

JF - Circulation. Genomic and precision medicine

SN - 1942-325X

IS - 6

ER -