title: Association of TNF-α Gene Variants With Clinical Manifestation of Cystic Fibrosis Patients of Iranian Azeri Turkish Ethnicity.
abstract: BACKGROUND
  Cystic fibrosis (CF), a life-limiting autosomal recessive disorder, is considered a monogenic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. According to several studies, mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene alone is insufficient to predict the phenotypic manifestations observed in cystic fibrosis (CF) patients. In addition, some patients with a milder CF phenotype do not carry any pathogenic mutation. Tumor Necrosis Factor-alpha (TNF-α) contributes to the pathophysiology of CF by causing cachexia. There is a reverse association between TNF-α concentration in patient's sputum and their pulmonary function.
  
  
  OBJECTIVE
  To assess the effect of non-CFTR genes on the clinical phenotype of CF, two polymorphic sites (-1031T/C and -308G/A) of the TNF-α gene, as a modifier, were studied.
  
  
  METHODS
  Focusing on the lung and gastrointestinal involvement as well as the poor growth, we first investigated the role of TNF-α gene in the clinical manifestation of CF. Furthermore, based on the hypothesis that the cumulative effect of specific alleles of multiple CF modiﬁer genes, such as TNF-α, may create the final phenotype, we also investigated the potential role of TNF-α in non-classic CF patients without a known pathogenic mutation. In all, 80 CF patients and 157 healthy control subjects of Azeri Turkish ethnicity were studied by the PCR-RFLP method. The chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis.
  
  
  RESULTS
  The allele and genotype distribution of the investigated polymorphisms, and their associated haplotypes were similar in all groups.
  
  
  CONCLUSIONS
  There was no evidence that supported the association of TNF-α gene polymorphisms with non-classic CF disease or the clinical presentation of classic CF.
authors.affiliation: Faculty of Natural Science, University of Tabriz, Tabriz, IR Iran.
authors.forename: Aziz
authors.initials: A
authors.lastname: Khorrami
authors.affiliation: Faculty of Natural Science, University of Tabriz, Tabriz, IR Iran.
authors.forename: Mortaza
authors.initials: M
authors.lastname: Bonyadi
authors.affiliation: Department of Pediatrics, Tabriz University of Medical Sciences, Tabriz, IR Iran.
authors.forename: Mandana
authors.initials: M
authors.lastname: Rafeey
authors.affiliation: Faculty of Natural Science, University of Tabriz, Tabriz, IR Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Omrani
keywords: Cystic Fibrosis; Gene; Tumor Necrosis Factor-alpha