Pterygium and genetic polymorphism of DNA double strand breakrepair gene Ku70

[摘要] Purpose: UV irradiation can produce a wide range of DNA damage,which will lead to gene mutation and uncontrolled cell proliferation. Ofthe many types of DNA damage, DNA double strand breaks (DSBs) are themost serious form, because of the intrinsic difficulty of their repair,inaccurate repair, or a lack of repair of DSBs can lead to mutations andlarge-scale genomic instability. DSBs are repaired by the DNA doublestrand break repair system. The DNA double strand break repair systemconsists of homologous recombination (HR) and nonhomologous end-joining(NHEJ). In humans, NHEJ is the predominant repair system and Ku70protein plays an initial and important role in the NHEJ system. Geneticpolymorphisms in NHEJ genes influence their DNA repair capacity andconfer predisposition to UV-induced skin cancer. Because pterygium is anUV-related uncontrolled cell proliferation, it is logical to assumepolymorphisms of Ku70 is associated with genetic predisposition topterygium.Methods: One hundred and twenty eight pterygium patients and 114volunteers without pterygium were enrolled in this study. Polymerasechain reaction based analysis was used to resolve the Ku70 promoterG-57C (rs2267437) and T-991C (rs5751129) polymorphisms.Results: There were significant differences between pterygium andcontrol groups in the distribution of genotype (p=0.013) and allelicfrequency (p=0.005) in the Ku70 promoter T-991C polymorphism.Individuals who carried at least one C allele (T/C and C/C) had a 2.83fold increased risk of developing pterygium compared to those whocarried the T/T wild type genotype (OR=2.83; 95% CI: 1.38-5.82).Moreover, individuals who carried at least one C allele (T/C and C/C)had a higher tendency to develop both sides of pterygium. In theKu70 promoter C-57G polymorphism, there was no difference betweenboth groups in the distribution of either genotype or allelicfrequency.Conclusions: The Ku70 promoter T-991C, but not the Ku70promoter C-57G polymorphism, is correlated with pterygium. The Ku70promoter T-991C polymorphism might become a potential marker for theprediction of pterygium susceptibility. It also provides a valuableinsight into the pathogenesis of pterygium.

[学科分类] 生物化学/生物物理