The prevalence of DNA base excision repair gene variants among the indigenous Abkhazian population

2021 ◽  
pp. 26-33
Author(s):  
С.В. Макаров ◽  
К.Б. Квеквескири
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Human Populations ◽  
Gene Variants ◽  
Ogg1 Gene ◽  
Arms Pcr ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Base Excision ◽  
Risk Of Cancer

Актуальность. Загрязнение окружающей среды промышленными отходами, токсическими агентами, опасными излучениями обусловливает возрастание мутационных процессов в биосфере, повреждений ДНК в клетках, рисков онкологических заболеваний. Жизнеспособность организма во многом зависит от наличия эффективных защитных средств против таких неблагоприятных факторов. Невозможность избежать повреждающих ДНК факторов экзогенного и эндогенного характера привела к возникновению более или менее эффективных репарационных систем, суть которых - элиминация первичных повреждений до их воплощения в мутационные события. У человека основным элементом одной из таких систем - эксцизионной репарации оснований ДНК является 8-оксогуанин-ДНК-гликозилаза (OGG1), противостоящая неблагоприятным последствиям оксидативного стресса. Ген OGG1 имеет вариации в кодирующей последовательности, частоты встречаемости которых могут различаться в разных этнических группах, но различаться может и эффективность функционирования продукта трансляции с такого транскрипта. Ser326Cys - яркий тому пример, замена аминокислотного остатка снижает эффективность репарационной функции, и носительство такой мутации, особенно в гомозиготном состоянии, чревато повышенным риском канцерогенеза и некоторыми другими неблагоприятными последствиями для здоровья. Цель. Исследование было направлено на установление частот встречаемости аллелей и генотипов полиморфизма rs1052133 гена OGG1, связанного с эксцизионной репарацией оснований, в популяции абхазов и сопоставление характера распределения с распространенностью в других популяциях Земного шара. Методы. В выборку для исследования абхазской популяции было включено 168 коренных жителей, постоянно проживающих на территории Абхазии. Генотипирование по полиморфизму Ser326Cys в экзоне 7 гена OGG1 (rs1052133) производилось методом ARMS-PCR-RFLP . Результаты. В выборке из абхазской популяции частота генотипа Ser/Ser составила 44,1%, Ser/Cys - 49,4 %, Cys/Cys - 6,5%. Частота аллеля OGG1*С (Ser) оказалась равной 0,688, а OGG1*G (Cys) достигла значения 0,312. Вывод. Частоты аллелей этого полиморфизма в популяции абхазов оказались близки к глобальным среднемировым значениям. Background. Environmental pollutions, toxic agents and dangerous radiation lead to increasing in levels of mutational processes, DNA damages and higher risks of cancer for bioorganisms. The life system viability depends on the effectiveness of the neutralizing the adverse factors. The unavoidance of the DNA damaging factors has led to developing the effective repair systems aimed to eliminate the primary damage. 8-oxoguanine-DNA glycosylase (OGG1) is the major element of the Base Excision Repair (BER) in human. The OGG1 gene has coding sequence variations spread with different frequencies in human populations. Ser326Cys is SNP with known defect in DNA repairing for Cys-allelomorph and an increased risk of cancer in the case. Objective. The study was aimed to estimate the prevalence OGG1 gene variants among the indigenous Abkhazian population and comparison with different ethnic groups worldwide. Methods. The study based on the analysis of 168 samples from Abkhazians. The OGG1 gene Ser326Cys genotyping was performed by the ARMS-PCR-RFLP . Results. The frequency stated for Ser/Ser genotype was 44.1%, Ser/Cys = 49.4 % and Cys/Cys = 6.5% in the Abkhazian population. Frequency of the OGG1 allele*C (Ser) was equal to 0.688, and OGG1*G (Cys) reached the value of 0.312. Conclusion. The frequencies of the rs1052133 alleles in the Abkhazian population were close to the global average values.

scholarly journals Association of Base Excision Repair Gene Polymorphisms with ESRD Risk in a Chinese Population

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Zhenming Cai ◽  
Huimei Chen ◽  
Jing Tao ◽  
Wenwen Guo ◽  
Xiufang Liu ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Maintenance Hemodialysis ◽  
Repair Gene ◽  
Dna Oxidative Damage ◽  
Increased Risk ◽  
Base Excision ◽  
Stage Renal Disease ◽  
End Stage

The base excision repair (BER) pathway, containingOGG1, MTH1andMUTYH, is a major protector from oxidative DNA damage in humans, while 8-oxoguanine (8-OHdG), an index of DNA oxidation, is increased in maintenance hemodialysis (HD) patients. Four polymorphisms of BER genes, OGG1 c.977C > G (rs1052133),MTH1c.247G > A (rs4866),MUTYHc.972G > C (rs3219489), andAluYb8MUTYH(rs10527342), were examined in 337 HD patients and 404 healthy controls. And the 8-OHdG levels in leukocyte DNA were examined in 116 HD patients. The distribution ofMUTYHc.972 GG orAluYb8MUTYHdiffered between the two groups and was associated with a moderately increased risk for end-stage renal disease (ESRD) (P=0.013and 0.034, resp.). The average 8-OHdG/106 dG value was significantly higher in patients with theOGG1c.977G,MUTYHc.972G orAluYb8MUTYHalleles (P<0.001via ANOVA). Further analysis showed that combination ofMUTYHc.972GG withOGG1c.977GG orAluYb8MUTYHincreased both the risk for ESRD and leukocyte DNA 8-OHdG levels in HD patients. Our study showed thatMUTYHc.972GG,AluYb8MUTYH, and combination ofOGG1c.977GG increased the risk for ESRD development in China and suggested that DNA oxidative damage might be involved in such process.

scholarly journals Inter-individual variation in DNA damage and base excision repair in young, healthy non-smokers: effects of dietary supplementation and genotype

2010 ◽  
Vol 103 (11) ◽  
pp. 1585-1593 ◽  
Author(s):  
Fiona Caple ◽  
Elizabeth A. Williams ◽  
Alison Spiers ◽  
John Tyson ◽  
Brian Burtle ◽  
...  
Keyword(s):  
Dna Damage ◽  
Base Excision Repair ◽  
Individual Variation ◽  
Manganese Superoxide Dismutase ◽  
Fruits And Vegetables ◽  
Excision Repair ◽  
Antioxidant Properties ◽  
Damage Level ◽  
Base Excision ◽  
Risk Of Cancer

Diets rich in fruits and vegetables are associated with lower risk of cancer which may be conferred in part by the antioxidant properties of these foods. However, antioxidant supplementation or increased consumption of antioxidant-rich foods has been reported to have inconsistent effects on DNA damage. The present work (the DART study) investigated the extent of inter-individual variation in DNA damage, the capacity for base excision repair (BER) and the responses of both variables to supplementation with an antioxidant supplement for 6 weeks. There was a wide inter-individual variation in endogenous lymphocyte DNA strand breaks (8-fold variation), in damage after a challenge with H2O2 (16-fold variation) and in DNA repair (41-fold variation) measured using the comet assay. When stratified into tertiles according to the pre-supplementation level of endogenous DNA damage, there was a statistically significant decrease in DNA damage after supplementation in the tertile with the highest pre-supplementation level of damage. There was no effect of supplementation on BER. Endogenous DNA damage level before supplementation was significantly different (P = 0·037) between the three genotypes for the Val16Ala single nucleotide polymorphism in manganese superoxide dismutase (rs4880) with individuals homozygous/wild type showing less damage than those carrying the alanine variant.

scholarly journals Analysis of Polymorphisms Associated with Base Excision Repair in Patients Susceptible and Resistant to Noise-Induced Hearing Loss

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Enmin Ding ◽  
Jiadi Guo ◽  
Xin Ge ◽  
Rongjian Sheng ◽  
Jian Chen ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Allele Frequency ◽  
Base Excision Repair ◽  
Significant Interaction ◽  
Excision Repair ◽  
Noise Induced Hearing Loss ◽  
Coding Region ◽  
Increased Risk ◽  
Base Excision ◽  
Sensitive Group

Objective. Noise-induced hearing loss (NIHL) is one of the most common occupational health risks in both developed and industrialized countries. It occurs as a result of interactions between genetic and environmental factors. Nevertheless, inherited genetic factors contributing to NIHL are not well understood. Therefore, we aim to investigate whether genetic mutations in three important base excision repair genes (OGG1, APEX1, and XRCC1) may influence susceptibility to NIHL. Methods. Three SNPs in OGG1, APEX1, and XRCC1 were genotyped from 1170 noise-exposed workers and were classified into 117 most susceptible and 117 most resistant individuals. Results. Results showed that the rs1799782 TT genotype located in the XRCC1 coding region and rs1130409 GG/GT in the APEX1 coding region were associated with increased risk for NIHL in a Chinese population. Compared to the rs1799782 C allele frequency, the T allele frequency was increased in the sensitive group (adjusted OR=1.51, 95%CI=1.01 to 2.26, P=0.043). The rs1130409 G allele frequency was also increased in the sensitive group compared to the resistant group (adjusted OR=1.59, 95%CI=1.10 to 2.31, P=0.015). Moreover, rs1130409 and drinking had a statistically significant interaction (P=0.0002), while rs1799782, rs1130409, and smoking also had a statistically significant interaction (P<0.0001). Conclusions. XRCC1 rs1799782 and APEX1 rs1130409 may have potential as biomarkers for the screening of susceptibility to NIHL in workers exposed severe noise.

scholarly journals Role for DNA base‐excision repair gene variants in the prognosis of Hodgkin lymphoma

2019 ◽  
Vol 186 (1) ◽  
pp. 171-175
Author(s):  
Vanessa Daniel ◽  
Marcia T. Delamain ◽  
Bruna de A. Murbach ◽  
Carmino A. Souza ◽  
Carmen S. P. Lima ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Gene Variants ◽  
Repair Gene ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision

scholarly journals Investigation of base excision repair gene variants in late-onset Alzheimer’s disease

PLoS ONE ◽  
2019 ◽  
Vol 14 (8) ◽  
pp. e0221362
Author(s):  
Tugce Ertuzun ◽  
Asli Semerci ◽  
Mehmet Emin Cakir ◽  
Aysegul Ekmekcioglu ◽  
Mehmet Oguz Gok ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Base Excision Repair ◽  
Late Onset ◽  
Excision Repair ◽  
Gene Variants ◽  
Repair Gene ◽  
Base Excision

scholarly journals Analysis of polymorphisms associated with base excision repair in patients susceptible and resistant to noise-induced hearing loss

2019 ◽  
Author(s):  
Enmin Ding ◽  
Jiadi Guo ◽  
Rongjian Sheng ◽  
Jian Chen ◽  
Hengdong Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Allele Frequency ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Noise Induced Hearing Loss ◽  
Coding Region ◽  
Increased Risk ◽  
Base Excision ◽  
Susceptibility To Noise ◽  
Sensitive Group

Abstract Objective We aim to investigate whether genetic mutations in three important base excision repair genes (OGG1, APEX1, and XRCC1) may influence susceptibility to noise-induced hearing loss. Methods Three SNPs in OGG1, APEX1, and XRCC1 were genotyped from noise exposed workers who were classified into susceptible and resistant individuals. Results: Results showed that the rs1799782 TT genotype located in the XRCC1 coding region and rs1130409 GG/GT in the APEX1 coding region were associated with increased risk for noise-induced hearing loss. Compared to the rs1799782 C allele frequency, the T allele frequency increased in the sensitive group (OR = 1.51). Rs1130409 G allele frequency also increased in the sensitive group compared to the resistant group (OR = 1.59). Conclusions XRCC1 rs1799782 and APEX1 rs1130409 may have potential as biomarkers for screening susceptibility to NIHL in workers exposed severe noise.

scholarly journals Germline loss-of-function variants in the base-excision repair gene MBD4 cause a Mendelian recessive syndrome of adenomatous colorectal polyposis and acute myeloid leukaemia

2021 ◽  
Author(s):  
Claire Palles ◽  
Edward Chew ◽  
Judith E. Grolleman ◽  
Sara Galavotti ◽  
Christoffer Flensburg ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Genetic Diagnosis ◽  
Adenomatous Polyposis ◽  
Loss Of Function ◽  
Driver Genes ◽  
Repair Gene ◽  
Colorectal Polyposis ◽  
Increased Risk ◽  
Base Excision

ABSTRACTInherited defects in base-excision repair (BER) predispose to adenomatous polyposis and colorectal cancer (CRC), yet our understanding of this important DNA repair pathway remains incomplete. By combining detailed clinical, histological and molecular profiling, we reveal biallelic germline loss-of-function (LOF) variants in the BER gene MBD4 to predispose to adenomatous polyposis and –uniquely amongst CRC predisposition syndromes– to myeloid neoplasms. Neoplasms from MBD4-deficient patients almost exclusively accumulate somatic CpG>TpG mutations, resembling mutational signature SBS1. MBD4-deficient adenomas harbour mutations in known CRC driver genes, although AMER1 mutations were more common and KRAS mutations less frequent. We did not find an increased risk for colorectal tumours in individuals with a monoallelic MBD4 LOF variant. We suggest that this condition should be termed MBD4-associated neoplasia syndrome (MANS) and that MBD4 is included in testing for the genetic diagnosis of polyposis and/or early-onset AML.

Modulation of Base Excision Repair Alters Cellular Sensitivity to UVA1 but not to UVB¶

2002 ◽  
Vol 75 (5) ◽  
pp. 507 ◽  
Author(s):  
Katherine J. Kim ◽  
Indraneel Chakrabarty ◽  
Guang-Zhi Li ◽  
Sabine Grösch ◽  
Bernd Kaina ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Cellular Sensitivity ◽  
Base Excision

Defective Base Excision Repair Associated with NTHL1

2019 ◽  
Vol 68 ◽  
Author(s):  
Richarda de Voer ◽  
Paul W Doetsch ◽  
Roland Kuiper ◽  
Barbara Rivera
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Base Excision
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