Association between polymorphisms of DNA repair genes and risk of type 2 diabetes mellitus in the Turkish population
-
Neslihan Tokmak
Abstract
Objectives
DNA repair mechanisms work insufficiently in T2DM patients and hyperglycemia seen in diabetes disturbs the oxidant-antioxidant balance thus cause oxidative damage on DNA. The effects of the DNA repair genes’ have not yet been investigated on diabetes. The aim of this study was to investigate the association between APE1 Asp148Glu and XPG Asp1104His polymorphisms with T2DM in the Turkish population.
Material and methods
Sixty-five T2DM patients and 54 healthy individuals were included to this study as control. The polymerase chain reaction-restriction fragment length polymorphism techniques were used.
Results
When the study groups were compared, serum HDL-cholesterol levels were found statistically elevated in the controls. Once the APE1 Asp148Glu polymorphism distribution between the patient and control groups was investigated, the Glu/Glu genotype ratio was found significantly higher in the control group. Furthermore, the Asp/Glu genotype and the Asp allele prevalences were observed to be higher in the patient group. Also, patients with the Asp/Asp genotype had higher serum HDL-cholesterol levels than the others.
Conclusion
Despite the small number of subjects included, it could be interpreted that the Glu allele of the APE1 Asp148Glu polymorphism might be protective against and the Asp allele may be contributing to the development of diabetes.
Özet
Amaç
T2DM hastalarının DNA tamir mekanizması düzgün çalışmamaktadır ve diyabette görülen hiperglisemi, organizmanın oksidan-antioksidan dengesini bozarak DNA’da oksidatif hasarlara sebep olmaktadır. DNA tamir genlerinin etkileri bugüne kadar diyabette çalışılmamıştır. Bu çalışmanın amacı, Türk toplumundaki T2DM’li hastalarda APE1 Asp148Glu ve XPG Asp1104His polimorfizmlerinin ilişkisini incelemektir.
Gereç ve Yöntem
Çalışmamıza 65 T2DM hastası ve kontrol grubu olarak da 54 sağlıklı birey dahil edildi. Polimorfizmlerin belirlenmesinde Polimeraz Zincir Reaksiyonu (PZR), Restriksiyon Parça Uzunluk Polimorfizmi (RFLP) teknikleri kullanılmıştır.
Bulgular
Serum HDL-kolesterol düzeyi bakımından gruplar karşılaştırıldığında hasta grubuna göre kontrol grubunda serum HDL-kolesterol düzeyinin istatistiksel olarak arttığı belirlenmiştir. Hasta ve kontrol grupları arasında APE1 Asp148Glu polimorfizmi genotip dağılımları incelendiğinde kontrol grubunda Glu/Glu genotipi taşıma oranının, hasta grubuna göre anlamlı olarak yüksek olduğu tespit edilmiştir. Hasta grubunda ise Asp/Glu genotipi ve Asp alleli tasıma oranının kontrol grubuna göre istatistiksel olarak arttığı gözlemlenmiştir. Ayrıca hasta grubunda Asp/Asp genotipi taşıyan bireylerde taşımayanlara göre serum HDL-kolesterol düzeyi anlamlı olarak yüksek olarak bulunmuştur.
Sonuç
Çalışmamıza dahil edilen örnek sayısı az olmasına rağmen, APE1 Asp148Glu polimorfizmi için Glu allelinin koruyucu olabileceğini ve Asp allelinin ise diyabet gelişiminde rol oynayabileceğini söyleyebiliriz.
Introduction
Diabetes mellitus (DM) develops due to insulin insufficiency, effects of altered insulin activity or both, and is defined as a metabolic disorder characterized with disrupted glucose tolerance and hyperglycemia [1]. Type 2 diabetes mellitus (T2DM) is the most common among all types of diabetes and as a result of the variety of the factors seen in phenotype, it is considered as a heterogenic disease [2]. Since its prevalence is rapidly rising worldwide, T2DM has become the most significant and formidable health problem of the 21st century [1].
The chronic hyperglycemia seen in T2DM leads to an increase in reactive oxygen species (ROS) and/or a reduction in antioxidant defense, meaning additional oxidative stress that induces oxidative damage on biomolecules such as lipids, proteins and DNA [3], [4]. Some complications of diabetes have been associated with increased activity of lipid peroxidation due to free radicals and accumulation of lipid peroxidation products [5]. DNA damage is a major reason for cellular functional disturbances and cell death, which plays an important part in the pathogenesis of diabetic complications [3]. Certain oxidative damages are highly associated with a considerable decrease in the antioxidant levels of the patient and the up regulation of the DNA damage as a result of pro-oxidants. Thus, this situation leads to attenuation in the efficiency of DNA repair mechanisms and increases the risk of cancer development [4], [6].
It has been shown that the DNA repair mechanisms of type 2 diabetes patients do not work properly. The increase of oxidative stress levels and also the decrease in the efficiency of DNA repair in T2DM both has significant contributions to neoplastic transformation [7]. The oxidative DNA damage encountered in diabetes is generally repaired by the base excision repair (BER) mechanisms, in which APE1 plays a vital role. The APE1 gene is located on chromosome 14q11.2-q12 where 18 polymorphisms have been described so far. Among these polymorphisms the most studied is the thymine to guanine transversion Asp148Glu polymorphism [8]. Moreover, disorders in nucleotide excision repair (NER) mechanism have also been shown in cancers of type 2 diabetes patients [9]. With its endonuclease activity, Xeroderma pigmentosum G (XPG) plays a key role in the restoration of the DNA helix structure in NER. The XPG gene is located on chromosome 13q22 and the ASP1104His polymorphism on exon 15 is associated with cancer development [10].
Recent studies on APE1 and XPG have mostly focused on a probable genetic susceptibility to cancer development yet their relation with diabetes has not been studied. In this study, the aim was to investigate the association between the APE1 Asp148Glu and XPG Asp1104His gene polymorphisms with T2DM.
Materials and methods
Study group
This study was conducted with the approval of the Istanbul Medical Faculty Ethical Committee, Istanbul University. Study group comprised of 65 patients (35 women, 30 men) diagnosed with T2DM and in follow up by the Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University and 54 healthy individuals (11 women, 43 men).
DNA isolation and SNP detection
Blood samples were obtained from the participants in EDTA containing 10 mL tubes and stored at −20°C until the DNA isolation step that was performed using the salting out method [11]. The specific primers shown in Table 1 were used to amplify the APE1 Asp148Glu and XPG Asp1104His polymorphisms gene regions for the PCR method. The PCR reaction volume was set as 25 μL as 1 μL DNA sample of 50–100 ng, 2.5 μL dNTP (100 μ/mL), 2 μL MgCl2 (25 mM/mL), 1 μL each primer and 0.5 μL Taq polymerase (5 U/μL), 1.5 μL 10X DNA Taq PCR buffer and 16.5 μL apyrogenic water. The PCR mix was prepared on ice and in a sterile cabin. The PCR reaction for APE1 Asp148Glu was set as 95°C for 30 s, 52°C for 45 s and 75°C for 45 s for 35 cycles following the 95°C for 2 min initial denaturation and a final elongation step as 72°C for 5 min. For the XPG Asp1104His polymorphism 94°C for 1 min, 62°C for 1 min and 72°C for 1 min for 35 cycles following the 95°C for 5 min initial denaturation and a final elongation step as 72°C for 10 min. The PCR yields were controlled on 3% agarose gel electrophoresis. In order to determine the APE1 Asp148Glu and XPG Asp1104His poly morphisms the PCR yields were digested with FspBI (BfaI) and Hin1II (NlaIII) restriction enzymes, respectively. The digested yields were separated on 3% agarose gel electrophoresis and genotyped after being viewed under UV light. Used primers and restriction enzymes and obtained PCR and restriction yields are given with their lengths and which genotype they correspond to in Table 1. The genotyping for APE1 Asp148Glu was evaluated as, AA for Asp/Asp, GG for Glu/Glu and AG for Asp/Glu, and for XPG Asp1104His GG for Asp/Asp, CC for His/His and GC for Asp/His.
PCR-RFLP-based assay of APE1 Asp148Glu and XPG Asp1104His polymorphisms.
| SNPs | Primers | Restriction enzymes | Interpretation (bp) |
|---|---|---|---|
| APE1 Asp148Glu | F: 5′-CTGTTTCATTTCTATAGGCTA-3′ R: 5′-AGGAACTTGCGAAAGGCTTC-3′ | FspBI (BfaI) | AA: 164 GG: 144+20 AG: 164+144+20 |
| XPG Asp1104His | F: 5′-GACCTGCCTCTCAGAATCATC-3′ R: 5′-CCTCGCACGTCTTAGTTTCC-3′ | Hin1II (NlaIII) | GG: 271 CC: 227+44 GC: 271+227+44 |
F, Forward primer; R, reverse primer.
Statistical analysis
The statistical analysis was performed using SPSS version 11.0 (SPSS Inc. Chicago, USA). For the determination of the distribution of the prevalence of the alleles between groups the Chi-squared (χ2) and Fisher’s test were used. The demographical data was compared using Student’s t-test and one way ANOVA. Allele frequencies were determined using the gene counting method. Values of p<0.05 were considered statistically significant.
Results
The mean age of the 65 patients included in this study were 59.93±13.97 and the 54 healthy controls were 54.83±10.88, which was compatible. When the serum HDL-cholesterol levels were compared, it was found higher in the control group than the patient group (p=0.001, 95%CI=3.51–11.97). The demographic data is given in Table 2.
Demographic details of the study groups.
| Demographic parameters | Control (n: 54) | Patient (n: 65) |
|---|---|---|
| Age (years) | 54.83±10.88 | 59.93±13.97 |
| Gender (F/M) | 11/43 | 35/30 |
| Body mass index (kg/m2) | 26.33±3.77 | 28.25±8.36 |
| Triglyceride (mg/dL) | 174.6±112.47 | 152.22±73.85 |
| Total cholesterol (mg/dL) | 198.98±46.14 | 187.25±69.45 |
| HDL-cholesterol (mg/dL) | 41.47±8.05a | 33.72±12.25 |
| LDL-cholesterol (mg/dL) | 129.73±42.39 | 113.41±39.81 |
| VLDL-cholesterol (mg/dL) | 31.58±17.89 | 32.02±18.97 |
| Blood glucose level (mg/dL) | – | 218.4±115.26 |
| HbA1c (%) | – | 24.2±8.73 |
| Insulin (mU/mL) | – | 13.44±10.43 |
| C-peptide (ng/mL) | – | 5.32±5.71 |
| Folate (ng/mL) | – | 7.3±3.29 |
| B12 (pg/mL) | – | 514.1±403.19 |
ap: 0.001, 95% CI: 3.51–11.97.
The mutant APE1 Asp148Glu Glu/Glu genotype was not encountered in the patient group thus the Glu/Glu genotype is found statistically higher in the control group (p=0.007, 95% CI=0.80–0.97). Also, the Asp/Glu genotype (p=0.005, χ2=8.005, OR=2.904, 95% CI=1.375–6.133) and the Asp allele (p=0.007, 95% CI=0.80–0.97) were found more common in the patient group (Table 3). According to our findings, it can be said that carrying the Asp genotype may be a risk factor for diabetes development. Once the study groups were compared for APE1 Asp148Glu polymorphism genotype distribution and lipid profiles, the Asp/Asp carriers in the patient group had significantly higher HDL-cholesterol levels (p=0.05). Since there were no patients carrying the Glu/Glu genotype, it could not be evaluated (Table 4).
The APE1 Asp148Glu genotype/allele distributions in the patient and control groups.
| APE1 Asp148Glu | Control (n: 54) | Patient (n: 65) | ||
|---|---|---|---|---|
| n | % | n | % | |
| Asp/Asp (AA) | 28 | 51.9 | 24 | 36.9 |
| Asp/Glu (AG) | 20 | 37 | 41 | 63.1b |
| Glu/Glu (GG) | 6 | 11.1a | 0 | 0 |
| Asp+ | 48 | 88.9 | 65 | 100c |
| Glu+ | 26 | 48.1 | 41 | 63.1 |
ap: 0.007, 95% CI: 0.80–0.97.
bp: 0.005, χ2: 8.005, OR: 2.904, 95% CI: 1.375–6.133.
cp: 0.007, 95% CI: 0.80–0.97.
Demographic data on APE1 Asp148Glu genotypes and lipid profiles.
| Groups | Patient (n: 65) | Control (n: 54) | ||||
|---|---|---|---|---|---|---|
| APE1 genotypes | Asp/Asp (n: 24) | Asp/Glu (n: 41) | Glu/Glu (n: 0) | Asp/Asp (n: 28) | Asp/Glu (n: 20) | Glu/Glu (n: 6) |
| Triglyceride (mg/dL) | 159.33±81.98 | 147.70±69.12 | 0 | 171.79±134.54 | 164.20±79.54 | 211.83±91.12 |
| Total cholesterol (mg/dL) | 188.14±53.63 | 186.71±78.42 | 0 | 192.83±42.95 | 200.40±53.39 | 220.00±39.4 |
| HDL-cholesterol (mg/dL) | 38.10±13.06a | 31.15±11.15 | 0 | 42.79±6.54 | 40.47±11.00 | 38.67±3.67 |
| LDL-cholesterol (mg/dL) | 120.74±45.91 | 109.09±35.78 | 0 | 129.62±43.69 | 126.00±41.34 | 139.50±45.78 |
| VLDL-cholesterol (mg/dL) | 31.86±16.39 | 32.13±20.69 | 0 | 28.58±18.87 | 33.40±16.56 | 39.0±17.1 |
ap: 0.05.
There was no significant difference between the patient and control groups in terms of XPG Asp110His poly morphism genotype distribution (Table 5). The association between the serum lipid profiles and XPG Asp1104His polymorphism genotypes in the patient and control groups are shown in Table 6. In the control group, Asp/Asp genotype carriers had higher HDL-cholesterol levels than the His/His carriers (p=0.025, 95% CI=1.29–18.11). There was only a single patient carrying a His/His genotype thus it could not be statistically evaluated.
The XPG Asp1104His genotype/allele distributions in the patient and control groups.
| XPG Asp1104His | Control (n: 54) | Patient (n: 65) | ||
|---|---|---|---|---|
| n | % | n | % | |
| Asp/Asp (GG) | 31 | 57.4 | 36 | 55.4 |
| Asp/His (GC) | 18 | 33.3 | 28 | 43.1 |
| His/His (CC) | 5 | 9.3 | 1 | 1.5 |
| Asp+ | 49 | 90.7 | 64 | 98.5 |
| His+ | 23 | 42.6 | 29 | 44.6 |
Demographic data on XPG Asp1104His genotypes and lipid profiles.
| Groups | Patient (n: 65) | Control (n: 54) | ||||
|---|---|---|---|---|---|---|
| XPG genotypes | Asp/Asp (n: 36) | Asp/His (n: 28) | His/His (n: 1) | Asp/Asp (n: 31) | Asp/His (n: 18) | His/His (n: 5) |
| Triglyceride (mg/dL) | 153.07±76.21 | 155.09±71.37 | 61 | 151.40±91.48 | 209.56±143.39 | 179.75±68.71 |
| Total cholesterol (mg/dL) | 196.0±83.43 | 176.30±45.81 | 168 | 194.24±47.16 | 207.88±46.19 | 193.0±45.92 |
| HDL-cholesterol (mg/dL) | 32.07±11.83 | 35.65±12.97 | 39 | 43.2±9.06a | 40.75±3.02 | 33.5±11.61 |
| LDL-cholesterol (mg/dL) | 116.19±42.68 | 109.63±37.29 | 116 | 128.68±48.92 | 132.25±35.49 | 126.25±29.31 |
| VLDL-cholesterol (mg/dL) | 33.46±22.07 | 31.01±14.27 | 12.20 | 29.72±18.04 | 34.0±19.45 | 33.5±11.67 |
ap: 0.025, 95% CI: 1.29–18.11.
Discussion
T2DM arises due to the gradual loss of pancreatic β cell function where the insulin hormone is secreted to balance the insulin resistance that leads to hyperglycemia [12]. Recent studies have shown that the increase in free radicals and the decrease in the antioxidant potential, which result with cellular oxidative damage, are associated with DM [3]. In the case of hyperglycemia, it is indicated that ROS production increases depending on the –OH radical formation, the result of glucose auto-oxidation [13]. High ROS production and accumulation leads to oxidative stress, therefore disrupts the physiologic function and the structure of the cellular biomolecules, and also impairs cell viability and functioning [12]. Oxidative stress debilitates the antioxidant mechanism of the body and in consequence causes DNA damage, lipid peroxidation and protein modifications. Subsequently, it leads to diabetes, atherosclerosis, chronic inflammation, cardiovascular diseases, cancer, and neurological diseases like Alzheimer’s and Parkinson’s [14]. As an important part of the BER mechanism, the APE1 enzyme repairs the oxidized and alkalized DNA’s 3′-hydroxylation damage by producing normal 3′-hydroxyl groups. Although there are 18 polymorphisms identified in APE1, the most widely studied is the Asp148Glu (T1349G) (rs3136820) [15]. In many different ethnic groups, the association between the APE1 Asp148Glu polymorphism with numerous cancer types has been studied. Gu et al. [15], in their meta-analysis including 27 studies showed that it might be a risk factor for cancer development. In other studies, the APE1Asp148Glu polymorphism was shown to be a possible risk factor for urinary cancers, hepatocellular carcinoma and breast cancer [16], [17], [18]. Migraine, myocardial infarction and Parkinson’s disease have also been associated, however, no association was found between Alzheimer’s disease and the APE1 Asp148Glu polymorphism [19], [20], [21], [22].
In this study, the Glu/Glu genotype of the APE1 Asp148Glu was not encountered in the patient group, therefore, due to this absence its prevalence seems significantly higher in the control group. The Asp/Glu genotype and the Asp allele carriers were higher in the patient group than the controls. Expanding the study population will clarify the data for the evaluation of the Asp allele as a risk factor for diabetes development. Patients with the Asp/Asp geno type were found to have significantly higher HDL-cholesterol levels than the controls. No other studies have been found investigating an association between type 2 diabetes and/or lipid profiles and the APE1 Asp148Glu polymorphism, which makes this study the first.
One of the SNPs found in XPG is the XPG Asp1104His polymorphism identified as the guanine to adenine transition, which results with the coding of the amino acid histidine instead of aspartic acid [23]. XPG Asp1104His polymorphism have been previously investigated in various cancers such as gastrointestinal cancers, head and neck cancer and leukemia. There was no association found with leukemia, yet it was indicated as a risk factor especially for larynx cancer in the Asian population [24], [25], [26]. In a meta-analysis of eight studies and another of 17 studies, the XPG Asp1104His polymorphism was shown not associated with breast cancer [27], [28]. In an additional meta-analysis it was indicated as a risk factor for melanoma [29]. Moreover, the XPG Asp1104His polymorphism has also been shown to have a positive association with Parkinson’s disease yet none with coronary artery disease [21], [30].
In this study, no significant relation was found with the XPG Asp1104His polymorphism between the study groups. Once the XPG genotypes and lipid profiles were evaluated, the Asp/Asp genotype carriers were observed to have significantly higher HDL-cholesterol levels than the His/His genotype carriers. No other studies have been found showing a relation between the XPG Asp1104His polymorphism and type 2 diabetes and/or lipid profiles. The limitation of this study is the small number of the study groups and it will be carried out further with a larger study group for greater statistical significance.
Acknowledgements
This study was supported by The Research Support Unit of Istanbul University, project no: 6545. In this study, the experimental work was carried out by Neslihan Tokmak as her Master’s Thesis in Istanbul University and it was proposed and guided by Prof. Dr. Sakir Umit Zeybek.
Conflict of interest: The authors declare that they have no conflict of interest.
References
1. van den Oever IA, Raterman HG, Nurmohamed MT, Simsek S. Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. Mediators Inflamm 2010;2010:792393.10.1155/2010/792393Search in Google Scholar PubMed PubMed Central
2. Rolo AP, Palmeira CM. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 2006;212:167–78.10.1016/j.taap.2006.01.003Search in Google Scholar PubMed
3. Kasznicki J, Krupa R, Blasiak J, Drzewoski J. Association between polymorphisms of the DNA repair genes XRCC1 and hOGG1 and type 2 diabetes mellitus in the Polish population. Pol Arch Med Wewn 2009;119:122–8.10.20452/pamw.626Search in Google Scholar
4. Sliwinska A, Blasiak J, Kasznicki J, Drzewoski J. In vitro effect of gliclazide on DNA damage and repair in patients with type 2 diabetes mellitus (T2DM). Chem Biol Interact 2008;173:159–65.10.1016/j.cbi.2008.03.017Search in Google Scholar PubMed
5. Gordon LA, Morrison EY, McGrowder DA, Young R, Fraser YT, Zamora EM, et al. Effect of exercise therapy on lipid profile and oxidative stress indicators in patients with type 2 diabetes. BMC Complement Altern Med 2008;13:21.10.1186/1472-6882-8-21Search in Google Scholar PubMed PubMed Central
6. Arif M, Islam MR, Waise TM, Hassan F, Mondal SI, Kabir Y. DNA damage and plasma antioxidant indices in Bangladeshi type 2 diabetic patients. Diabetes Metab 2010;36:51–7.10.1016/j.diabet.2009.05.007Search in Google Scholar PubMed
7. Maynard S, Schurman SH, Harboe C, de Souza-Pinto NC, Bohr VA. Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis 2009;30:2–10.10.1093/carcin/bgn250Search in Google Scholar PubMed PubMed Central
8. Gu D, Wang M, Wang S, Zhang Z, Chen J. The DNA repair gene APE1 T1349G polymorphism and risk of gastric cancer in a Chinese population. PLoS One 2011;6:e28971.10.1371/journal.pone.0028971Search in Google Scholar PubMed PubMed Central
9. Sliwinska A, Sliwinski T, Kasznicki J, Drzewoski J. Effect of gliclazide on nucleotide excision repair (NER) and non-homologous DNA end joining (NHEJ) in normal and cancer cells. J Physiol Pharmacol 2010;61:347–53.Search in Google Scholar
10. Emmert S, Schneider TD, Khan SG, Kraemer KH. The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms. Nucleic Acids Res 2001;29:1443–52.10.1093/nar/29.7.1443Search in Google Scholar PubMed PubMed Central
11. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.10.1093/nar/16.3.1215Search in Google Scholar PubMed PubMed Central
12. Acharya JD, Ghaskadbi SS. Islets and their antioxidant defense. Islets 2010;2:225–35.10.4161/isl.2.4.12219Search in Google Scholar PubMed
13. Golbidi S, Badran M, Laher I. Diabetes and alpha lipoic acid. Front Pharmacol 2011;2:69.10.3389/fphar.2011.00069Search in Google Scholar PubMed PubMed Central
14. Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology 2011;283:65–87.10.1016/j.tox.2011.03.001Search in Google Scholar PubMed
15. Gu D, Wang M, Wang M, Zhang Z, Chen J. The DNA repair gene APE1 T1349G polymorphism and cancer risk: a meta-analysis of 27 case-control studies. Mutagenesis 2009;24:507–12.10.1093/mutage/gep036Search in Google Scholar PubMed
16. Zhong JH, Zhao Z, Liu J, Yu HL, Zhou JY, Shi R. Association between APE1 Asp148Glu polymorphism and the risk of urinary cancers: a meta-analysis of 18 case-control studies. Onco Targets Ther 2016;9:1499–510.10.2147/OTT.S101456Search in Google Scholar PubMed PubMed Central
17. Yang Z, Zhao J. Effect of APE1 and XRCC1 gene polymorphism on susceptibility to hepatocellular carcinoma and sensitivity to cisplatin. Int J Clin Exp Med 2015;8:9931–6.Search in Google Scholar
18. AlMutairi F, Pathan AA, Alanazi M, Shalaby M, Alabdulkarim HA, Alamri A, et al. Association of DNA repair gene APE1 Asp148Glu polymorphism with breast cancer risk. Dis Markers 2015;2015:869512.10.1155/2015/869512Search in Google Scholar PubMed PubMed Central
19. Cetinkaya Y, Dasdemir S, Gencer M, Bireller ES, Ozkok E, Aydin M, et al. DNA repair gene variants in migraine. Genet Test Mol Biomarkers 2014;18:568–73.10.1089/gtmb.2014.0037Search in Google Scholar PubMed
20. Tekeli A, Isbir S, Ergen A, Gormus U, Bozkurt N, Timirci O, et al. APE1 and XRCC3 polymorphisms and myocardial infarction. In Vivo 2008;22:477–9.Search in Google Scholar
21. Gencer M, Dasdemir S, Cakmakoglu B, Cetinkaya Y, Varlibas F, Tireli H, et al. DNA repair genes in Parkinson’s disease. Genet Test Mol Biomarkers 2012;16:504–7.10.1089/gtmb.2011.0252Search in Google Scholar PubMed
22. Parildar-Karpuzoglu H, Dogru-Abbasoglu S, Hanagasi HA, Karadag B, Gurvit H, Emre M, et al. Single nucleotide polymorphisms in base-excision repair genes hOGG1, APE1 and XRCC1 do not alter risk of Alzheimer’s disease. Neurosci Lett 2008;442:287–91.10.1016/j.neulet.2008.07.047Search in Google Scholar PubMed
23. Berhane N, Sobti RC, Mahdi SA. DNA repair genes polymorphism (XPG and XRCC1) and association of prostate cancer in a north Indian population. Mol Biol Rep 2012;39:2471–9.10.1007/s11033-011-0998-5Search in Google Scholar PubMed
24. Yu G, Wang J, Dong J, Liu J. XPC Ala499Val and XPG Asp1104His polymorphisms and digestive system cancer risk: a meta-analysis based on model-free approach. Int J Clin Exp Med 2015;8:6621–30.Search in Google Scholar
25. Jiang HY, Zeng Y, Xu WD, Liu C, Wang YJ, Wang YD, et al. Genetic association between the XPG Asp1104His polymorphism and head and neck cancer susceptibility: evidence based on a meta-analysis. Asian Pac J Cancer Prev 2015;16:3645–51.10.7314/APJCP.2015.16.9.3645Search in Google Scholar PubMed
26. Douzi K, Ouerhani S, Menif S, Safra I, Abbes S. Polymorphisms in XPC, XPD and XPG DNA repair genes and leukemia risk in a Tunisian population. Leuk Lymphoma 2015;56:1856–62.10.3109/10428194.2014.974045Search in Google Scholar PubMed
27. Xu XM, Xie LC, Yuan LL, Hu XL, Jin JQ, Niu YM. Association of xeroderma pigmentosum complementation group G Asp1104His polymorphism with breast cancer risk: a cumulative meta-analysis. Mol Clin Oncol 2014;2:1177–81.10.3892/mco.2014.384Search in Google Scholar PubMed PubMed Central
28. Ding DP, He XF, Zhang Y. Lack of association between XPG Asp1104His and XPF Arg415Gln polymorphism and breast cancer risk: a meta-analysis of case-control studies. Breast Cancer Res Treat 2011;129:203–9.10.1007/s10549-011-1447-9Search in Google Scholar PubMed
29. Xu Y, Jiao G, Wei L, Wang N, Xue Y, Lan J, et al. Current evidences on the XPG Asp1104His polymorphism and melanoma susceptibility: a meta-analysis based on case-control studies. Mol Genet Genomics 2015;290:273–9.10.1007/s00438-014-0917-2Search in Google Scholar PubMed
30. Gokkusu C, Cakmakoglu B, Dasdemir S, Tulubas F, Elitok A, Tamer S, et al. Association between genetic variants of DNA repair genes and coronary artery disease. Genet Test Mol Biomarkers 2013;17:307–13.10.1089/gtmb.2012.0383Search in Google Scholar PubMed
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Articles in the same Issue
- Frontmatter
- Research Articles
- A Src/Abl kinase inhibitor, bosutinib, downregulates and inhibits PARP enzyme and sensitizes cells to the DNA damaging agents
- Effects of chromium picolinate on the parameters of oxidative and chromosomal DNA damage in rabbits
- Glucagon-like peptide-1 affects human umbilical vein endothelial cells in high glucose by the PI3K/Akt/eNOS signaling pathway
- Evaluation of apoptotic caspase levels in estimation of the wound age
- Use of immunohistochemical versus microsatellite analyses as markers for colorectal cancer
- Estimation of the Y-chromosomal short tandem repeat (Y-STR) mutation rates in Turkey
- Synthesis and evaluation of new benzimidazole derivatives with hydrazone moiety as anticancer agents
- Effects of chemoradiotherapy on acute-phase protein levels in glioblastoma multiforme and locally advanced non-small cell lung cancer
- Association between polymorphisms of DNA repair genes and risk of type 2 diabetes mellitus in the Turkish population
- Letter to the Editor
- Association of CTLA-4 polymorphisms and autoimmune type-1 diabetes mellitus susceptibility in Pakistani population
- Research Articles
- The effects of royal jelly on the oxidant-antioxidant system in rats with N-methyl-N-nitrosourea-induced breast cancer
- Meta-analysis of the relationship between MnSOD polymorphism and cancer in the Turkish and Cypriot population
- Resveratrol induces cell cycle arrest and apoptosis in epithelioid malignant pleural mesothelioma cells
