The Tumor Necrosis Factor α (-308 A/G) Polymorphism Is Associated with Cystic Fibrosis in Mexican Patients

Celia N Sanchez-Dominguez,Ricardo M Cerda-Flores,Hugo A Barrera-Saldaña,Hugo L Gallardo-Blanco,Maria Del C Villalobos-Torres,Miguel A Reyes-Lopez,Herminia G Martinez-Rodriguez,Rocio Ortiz-Lopez,Adriana Bustamante,Augusto Rojas-Martinez,Amit Gaggar

doi:10.1371/journal.pone.0090945

Celia N Sanchez-Dominguez, Ricardo M Cerda-Flores + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0090945

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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.ResultsThe 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.ConclusionAn 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.

Highlights

Gene-environment and gene-gene interactions play a role in the phenotypic expression of genetic diseases in individuals harboring the same genotype [1]
An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with Cystic fibrosis (CF) in Mexican patients
The mannose binding lectin (MBL2) gene encodes a serum acutephase protein secreted by the liver, resembling the complement component C1q, that leads to opsonization and activation of the complement system through the classical pathway [4]

Summary

Introduction

Gene-environment and gene-gene interactions play a role in the phenotypic expression of genetic diseases in individuals harboring the same genotype [1]. 1900 mutations and variants have been reported in the CF transmembrane conductance regulator (CFTR) gene, with DF508 being the most prevalent mutation Variants in genes that are involved in the inflammatory response have been studied in CF patients based on their potential effects on inflammation and host defense mechanisms. The serum concentration and complement-triggering activity of MBL depend on single-base mutations in the MBL2 gene [5,6,7]. These mutations may increase the susceptibility of carriers to colonization by bacterial and viral pathogens [8].

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