Polymorphisms of DNA base‐excision repair genes APE/Ref‐1 and XRCC1 are not associated with the risk for Graves' disease

Abstract

Oxidative stress has been implicated in etiopathogenesis of Graves' disease (GD). Increased lipid peroxidation and oxidative DNA damage have been found in GD patients. Oxidative DNA damage is mainly repaired by the base-excision repair (BER) pathway. Polymorphisms in DNA-repair genes have been associated with the increased risk of various diseases and could also be related to the etiology of GD. Therefore, we conducted a study including 197 patients with GD and age- and sex-matched 303 healthy subjects to examine the role of single-nucleotide polymorphisms of BER genes, APE/Ref-1 (codon 148) and XRCC1 (codons 194 and 399) as a risk factor for GD. These polymorphisms were determined by quantitative real-time PCR and melting curve analysis using LightCycler. No significant association was observed between the variant alleles of APE/Ref-1 codon 148 [odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.69-1.17], XRCC1 codon 194 (OR = 1.24, 95% CI = 0.79-1.94), and XRCC1 codon 399 (OR = 1.12, 95% CI = 0.86-1.46) and GD. These preliminary results suggest that APE/Ref-1 (codon 148) and XRCC1 (codons 194 and 399) polymorphisms are not significant risk factors for developing GD.

The 8‐oxoguanine DNA N‐glycosylase 1 (hOGG1) Ser326Cys variant affects the susceptibility to Graves' disease

“…There is considerable evidence of an imbalance between prooxidant–antioxidant status7–10 and increased oxidative DNA damage in patients having GD 11–15. Following these observations, in our previous study, we investigated the polymorphisms of APE/Ref‐1 and XRCC1, which are very important members of BER pathway and did not find an association between these polymorphisms and the GD risk 16. In the present study, we have focused to investigate hOGG1 Ser326Cys polymorphism (rs1052133) as a candidate risk factor for GD because, among DNA bases, guanine is the most vulnerable to ROS attack in GD, with 8‐oxoG being the major damage.…”

“…A total of 248 previously treated GD patients were included in this study (Table 1). GD was diagnosed on the basis of clinical and laboratory evidence as previously described 16. All patients were euthyroid at the time of evaluation for genetic polymorphism.…”

“…All patients were euthyroid at the time of evaluation for genetic polymorphism. The control group consisted of 303 individuals matched for age and sex 16. The study plan was approved by our institutional ethical committee, and informed consent was obtained for all patients and control subjects.…”

Modulation of trinucleotide repeat instability by DNA polymerase β polymorphic variant R137Q

“…polymorphism of DNA repair enzymes and cofactors, 8-oxoguanine DNA glycosylase (OGG1) [48, 49], APE1 [50], X-ray repair cross-complementing protein 1 (XRCC1) [51–53], XPC [54, 55], MSH3 [56–59], RPA-CDK7 [60] among others have been reported to be associated with cancer and neurodegenerative diseases. However, some studies do not support the notion [61–63]. The controversy is due to lack of knowledge of the effects of these BER polymorphic variants on genome stability and integrity.…”

Trinucleotide Repeat Instability Modulated by DNA Repair Enzymes and Cofactors

“…polymorphism of DNA repair enzymes and cofactors, 8oxoguanine DNA glycosylase (OGG1) [59,213], APE1 [214], X-ray repair crosscomplementing protein 1 (XRCC1) [215][216][217], XPC [218,219], MSH3 [220][221][222][223], RPA-CDK7 [224] among others have been reported to be associated with cancer and neurodegenerative diseases. However, some studies do not support the notion [225][226][227].…”