DNA damage and related modifier genes in Italian cystic fibrosis patients.
Cystic Fibrosis (CF) is an autosomal recessive multisystemic disorder showing a highly heterogeneous phenotype, even among siblings carrying identical CFTR mutations. Moreover, oxidative stress is of central importance in the pathogenesis of cystic fibrosis. The present study seeks to value the presence of oxidative damage in CF patients and the possible modifier effect of repair and glutathione-S-transferase genes. We analysed the presence of DNA damage in leukocytes of 63 CF patients at an Italian CF centre and 63 controls, through the alkaline Comet assay to detect DNA strand breaks. Furthermore, controls and 93 CF subjects were genotyped for 5 genes by RFLP-PCR (XRCC1,0GG1,GSTP1) and PCR assay (GSTM1, GSTT1). No difference in Comet assay values was observed comparing controls to CF patients, although CF subjects showed slightly higher mean values. The crude Odds-Ratio (OR) was higher than one for XRCC1 and GSTP1 genotypes and liver status and for XRCC1 and OGG1 genotypes and pancreatic insufficiency, but in all cases the p-values were not significant. In this case-control study, neither DNA damage ñor gene polymorphisms seem to influence CF manifestation.
Sezione di Tossicologia e Scienze Biomediche, ENEA Casaccia, Roma, Italia.
Silvia
S
Sterpone
Tommaso
T
Cornetta
Adriano
A
Angioni
Ersilia
E
Fiscarelli
Vincenzina
V
Lucidi
Antonella
A
Testa
Renata
R
Cozzi
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020552:Comet Assay; D003550:Cystic Fibrosis / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D005982:Glutathione Transferase; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human