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Annals of Hematology

, Volume 97, Issue 9, pp 1683–1687 | Cite as

− 174 G>C IL-6 polymorphism and primary iron overload in male patients

  • Walter F. Tetzlaff
  • Tomás Meroño
  • Eliana E. Botta
  • Maximiliano E. Martín
  • Patricia B. Sorroche
  • Laura E. Boero
  • Marcelo Castro
  • Gustavo D. Frechtel
  • Jorge Rey
  • Jorge Daruich
  • Gloria E. Cerrone
  • Fernando Brites
Original Article

Abstract

Primary iron overload (IO) is commonly associated with mutations in the hereditary hemochromatosis gene (HFE). Nonetheless, other genetic variants may influence the development of IO beyond HFE mutations. There is a single nucleotide polymorphism (SNP) at − 174 G>C of the interleukin (IL)-6 gene which might be associated with primary IO. Our aim was to study the association between the SNP − 174 G>C gene promoter of IL-6 and primary IO in middle-aged male patients. We studied 37 men with primary IO diagnosed by liver histology. Controls were age-matched male volunteers (n = 37). HFE mutations and the SNP − 174 G>C gene promoter of IL-6 were evaluated by PCR-RFLP. Logistic regression was used to evaluate the association between primary IO and SNP − 174 G>C gene promoter of IL-6. Patients and control subjects were in Hardy-Weinberg equilibrium for the SNP − 174 G>C gene promoter of IL-6 (p = 0.17). Significantly different genotype frequencies were observed between patients (43% CC, 43% CG, and 14% GG) and control subjects (10% CC, 41% CG, and 49% GG) (OR = 4.09, 95% CI = 2.06–8.13; p < 0.0001). The multiple logistic regression analysis showed that IO was significantly associated with CC homozygosis in the SNP − 174 G>C gene promoter of IL-6 (OR = 6.3, 95% CI = 1.9–21.4; p < 0.005) in a model adjusted by age and body mass index. In conclusion, CC homozygosis in the SNP − 174 G>C gene promoter of IL-6 can be proposed as one of the gene variants influencing iron accumulation in male adults with HFE mutations. Studies in larger cohorts are warranted.

Keywords

Iron overload Inflammation IL-6 Polymorphism HFE Hemochromatosis 

Notes

Acknowledgements

The authors wish to acknowledge the collaboration from the members of the Hospital de Clínicas “José de San Martín”, University of Buenos Aires.

Author contribution

Walter Tetzlaff, Tomas Meroño, Laura Boero, Eliana Botta, Maximiliano Martin, and Patricia Sorroche performed biochemical determinations and lipoprotein analyses. Walter Tetzlaff, Tomas Meroño, Laura Boero, Gloria Cerrone, Gustavo Frechtel, Fernando Brites, Jorge Rey, and Jorge Daruich contributed to the protocol design and data analysis. Jorge Daruich recruited patients and performed their clinical evaluation. Walter Tetzlaff, Marcelo Castro, Jorge Rey, Gloria Cerrone, and Gustavo Frechtel performed genetic testing. Walter Tetzlaff, Tomas Meroño, Gustavo Frechtel, Gloria Cerrone, and Fernando Brites contributed to writing the manuscript.

Funding

This work was supported in part by grants from the University of Buenos Aires (UBACyT CB23), CONICET (PIP 11220110100516), and National Agency for Scientific and Technological Promotion (PICT 2012-0418).

Compliance with ethical standards

The present study was carried out in accordance with the Declaration of Helsinki and the protocol was approved by the Ethics Review Board from the “José de San Martín” Clinical Hospital and from the Faculty of Pharmacy and Biochemistry, University of Buenos Aires.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Walter F. Tetzlaff
    • 1
    • 2
  • Tomás Meroño
    • 1
    • 2
  • Eliana E. Botta
    • 1
    • 2
    • 3
  • Maximiliano E. Martín
    • 1
    • 2
  • Patricia B. Sorroche
    • 4
  • Laura E. Boero
    • 1
    • 2
  • Marcelo Castro
    • 2
    • 5
  • Gustavo D. Frechtel
    • 6
  • Jorge Rey
    • 2
    • 5
  • Jorge Daruich
    • 7
  • Gloria E. Cerrone
    • 6
    • 8
  • Fernando Brites
    • 1
    • 2
    • 3
  1. 1.Laboratorio Lípidos y Aterosclerosis, Departamento de Bioquímica Clínica, Facultad de Farmacia y BioquímicaUniversidad de Buenos AiresBuenos AiresArgentina
  2. 2.Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto Fisiopatología y Bioquímica Clínica (INFIBIOC)Buenos AiresArgentina
  3. 3.Consejo Nacional de Investigación Científicas y Técnicas (CONICET)Buenos AiresArgentina
  4. 4.Hospital Italiano de Buenos Aires, Laboratorio CentralBuenos AiresArgentina
  5. 5.Hospital de clínicas “José de San Martín”, Departamento de Hemoterapia y Inmunohematología, División de Transfusión y Transmisión de enfermedadesUniversidad de Buenos AiresBuenos AiresArgentina
  6. 6.CONICET, Instituto de Inmunología, Genética y Metabolismo (INIGEM), Laboratorio de Diabetes y MetabolismoUniversidad de Buenos AiresBuenos AiresArgentina
  7. 7.Hospital de clínicas “José de San Martín”, Servicio de GastroenterologíaUniversidad de Buenos AiresBuenos AiresArgentina
  8. 8.Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Catedra de GenéticaUniversidad de Buenos AiresBuenos AiresArgentina

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