The tumor necrosis factor α (-308 A/G) polymorphism is associated with cystic fibrosis in Mexican patients

PLoS One. 2014 Mar 6;9(3):e90945. doi: 10.1371/journal.pone.0090945. eCollection 2014.

Abstract

Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (-251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP.

Results: The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25-9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease.

Conclusion: An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / pathology
  • Female
  • Gene Frequency
  • Genes, Modifier*
  • Genotype
  • Humans
  • Interleukin-8 / genetics
  • Male
  • Mannose-Binding Lectin / genetics
  • Mexico
  • Models, Genetic
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Tumor Necrosis Factor-alpha / genetics*
  • alpha 1-Antitrypsin / genetics

Substances

  • Interleukin-8
  • MBL2 protein, human
  • Mannose-Binding Lectin
  • SERPINA1 protein, human
  • Tumor Necrosis Factor-alpha
  • alpha 1-Antitrypsin

Grants and funding

This work was supported by grants from the Consejo Nacional de Ciencia y Tecnología CONACyT (62291 and 48497) and UANL’s PAICyT (1648-07) for ROL, Fondo Mixto de Fomento a la Investigación Científica y Tecnológica CONACYT – Gobierno del Estado de Tamaulipas (73578) and SIP-IPN (20080682) for MARL. The authors gratefully acknowledge scholarships from CONACyT, PIFI-IPN and Universia Santander for CNSD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.