title: Genetic Polymorphism and Messenger Ribonucleic Acid Concentrations of TNFα and TGFβ Genes in Patients with Chronic Lower Limb Infections.
abstract: BACKGROUND
  The number of chronic lower limb infections and their complications as venous and diabetic ulcers and chronic calf dermatitis is increasing worldwide. The clinical course and outcome in the immune responses to infection have been shown to be associated with genetic polymorphisms. The aim of study was to investigate frequencies of chosen single nucleotide polymorphisms (SNPs) in TNFα and TGFβ genes in patients with chronic lower limb infections and evaluate expression of messenger ribonucleic acid (mRNA) concentrations in chronic leg ulcers.
  
  
  METHODS
  Patients were divided into three groups: (group A) chronic venous leg ulcers, (group B) chronic post-traumatic non-healing wounds, and (group C) infected ischemic necrosis of the foot. Blood donors comprised the control group. Detection of polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene expression by real-time PCR methods.
  
  
  RESULTS
  Patients in all groups showed higher frequency of TNFα gene polymorphism -308GG and lower frequency of -308GA genotypes than controls. The mutated homozygote AA was higher in groups A and B than in controls. The TGFβ74GG genotype was represented at highest values in group B. The GC genotype was found in all groups at a similar concentration lower than in controls. Genotypes TGFβ29TT and TC were represented at similar concentrations as controls. Analyses showed that the presence of the polymorphic allele -308A of TNFα gene was correlated with an increased concentration of gene expression in patients with chronic leg ulcers (group A). In the case of both TGFβ gene polymorphisms the presence of polymorphic allele C resulted in increased TGFβ gene expression.
  
  
  CONCLUSIONS
  Comparison of genotypes in polymorphic sites in TNFα and TGFβ genes with their expression concentrations showed that the presence of polymorphic alleles could predispose to increased production of their proteins. Patients with prolonged non-healing wounds should have their genotypes studied, and in cases of mutation, long-term antibiotic and immune protein supply should be considered.
authors.affiliation: 1 Department of Surgical Research & Transplantology, Medical Research Centre , Polish Academy of Sciences, Warsaw, Poland .|2 Central Clinical Hospital , Ministry of Internal Affairs, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zagozda
authors.affiliation: 1 Department of Surgical Research & Transplantology, Medical Research Centre , Polish Academy of Sciences, Warsaw, Poland .|2 Central Clinical Hospital , Ministry of Internal Affairs, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sarnecka
authors.affiliation: 1 Department of Surgical Research & Transplantology, Medical Research Centre , Polish Academy of Sciences, Warsaw, Poland .|3 College of Inter-Faculty Individual Studies in Mathematics and Natural Sciences, Warsaw University , Warsaw, Poland .
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Staszczak
authors.affiliation: 1 Department of Surgical Research & Transplantology, Medical Research Centre , Polish Academy of Sciences, Warsaw, Poland .
authors.forename: Hanna
authors.initials: H
authors.lastname: Gałkowska
authors.affiliation: 2 Central Clinical Hospital , Ministry of Internal Affairs, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Andziak
authors.affiliation: 1 Department of Surgical Research & Transplantology, Medical Research Centre , Polish Academy of Sciences, Warsaw, Poland .|2 Central Clinical Hospital , Ministry of Internal Affairs, Warsaw, Poland.|4 Department of Human Epigenetics, Medical Research Centre , Polish Academy of Sciences, Warsaw, Poland .
authors.forename: Waldemar L
authors.initials: WL
authors.lastname: Olszewski
authors.affiliation: 1 Department of Surgical Research & Transplantology, Medical Research Centre , Polish Academy of Sciences, Warsaw, Poland .|2 Central Clinical Hospital , Ministry of Internal Affairs, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Durlik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D035002:Lower Extremity / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D018461:Soft Tissue Infections / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha