title: Associations of DNA-repair gene polymorphisms with a genetic susceptibility to ionizing radiation in residents of areas with high radon (222Rn) concentration.
abstract: OBJECTIVE
  To investigate the individual radiosensitivity of the human genome in long-term residents of areas with high radon concentration.
  
  
  METHODS
  The materials used for this investigation were venous blood samples extracted from children living in the boarding school of Tashtagol (Kemerovo Region, Russia). Cytogenetic damage assessment was performed using the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes. PCR, gel electrophoresis and product detection using a transilluminator were used to determine polymorphisms in the genes ADPRT (rs 1136410), hOGG1 (rs 1052133), NBS1 (rs 1805794), XRCC1 (rs 25487), XpC (rs 2228001), XpD (rs 13181), and XpG (rs 17655). Statistical analysis was performed using nonparametric methods. To ensure accurate results, FDR-correction for multiple comparisons was performed.
  
  
  RESULTS
  We discovered a significant increase in the frequency of binucleated lymphocytes with micronuclei (MN) in carriers of the His/His genotype of the XpG gene Asp1104His polymorphism in comparison to heterozygous and homozygous carriers of the Asp allele. In addition, the Ala/Ala genotype for the ADPRT gene Val762Ala polymorphism and the Glu/Gln genotype for the NBS1 gene Glu185Gln polymorphism were associated with the elevated frequency of binucleated lymphocytes with nucleoplasmic bridges (NPB).
  
  
  CONCLUSIONS
  As a result of this study, the elevated frequency of cytogenetic damage in people with particular DNA-repair gene polymorphisms in response to chronic exposure to radon was demonstrated. It was shown that the genes and corresponding polymorphisms (the XpG gene Asp1104His polymorphism, the ADPRT gene Val762Ala polymorphism and the NBS1 gene Glu185Gln polymorphism) can be used as molecular genetic markers of increased individual radiosensitivity in long-term residents of areas with high concentrations of radon.
authors: Department of Genetics, Biology Faculty, Kemerovo State University , Kemerovo , Russian Federation.
authors: Maxim Y
authors: MY
authors: Sinitsky
authors: Aleksey V
authors: AV
authors: Larionov
authors: Maxim A
authors: MA
authors: Asanov
authors: Vladimir G
authors: VG
authors: Druzhinin
mesh_terms: D000293:Adolescent; D000396:Air Pollutants, Radioactive / Q000009:adverse effects*; D019943:Amino Acid Substitution; D018797:Cell Cycle Proteins / Q000235:genetics; D002648:Child; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015162:Micronucleus Tests; D009687:Nuclear Proteins / Q000235:genetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011836:Radiation Tolerance / Q000235:genetics*; D011886:Radon / Q000009:adverse effects*; D012426:Russia; D014157:Transcription Factors / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D000396:Air Pollutants, Radioactive; D018797:Cell Cycle Proteins; D045647:DNA Glycosylases; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011886:Radon; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C112156:NBN protein, human; C000619371:XRCC1 protein, human; C086984:XPC protein, human; C499320:PARP1 protein, human; C479058:oxoguanine glycosylase 1, human; C497292:ERCC2 protein, human
keywords: DNA-repair; Micronuclei; genetic susceptibility; ionizing radiation; micronucleus test; radon