The novel allele (3R) of the VNTR polymorphism in the XRCC5 promoter region dramatically decreases the gene expression

Rajaei, Mehrdad; Saadat, Iraj; Saadat, Mostafa

doi:10.1016/j.bbrc.2012.11.099

Cited by 10 publications

(6 citation statements)

References 9 publications

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“…The XRCC 5 VNTR polymorphism, rs6147172, was located in the promoter region and could affect the transcriptional activity of this gene [27, 41]. Polymorphism of rs6147172 has been implicated in susceptibility to several cancers including bladder cancer [27], acute myeloid leukemia (AML) [26], chronic myeloid leukemia (CML) [23], and autoimmune disease such as SLE [30].…”

Section: Discussionmentioning

confidence: 99%

“…The promoter region of XRCC5 contains several copies of Sp1 recognition cis regulatory elements and its gene expression has Sp1-dependent manner (Figure 3(b)) [27, 43]. The VNTR polymorphism of XRCC5 can alter the number of Sp1 elements so that four different alleles of XRCC 5 VNTR 3R, 2R, 1R, and 0R possess eight, seven, six, and five copies of Sp1 elements, respectively [41], which were able to modify the expression of XRCC5 [27, 43]. The in silico analysis of present study showed that the presence of tandem repeats in XRCC5 gene promoter can be sequenced to bind to more nuclear factors and probably affect transcriptional activity (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

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XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with Male Infertility Risk: Evidences from Case-Control and In Silico Studies

Jahantigh

Colagar

2017

International Journal of Endocrinology

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We evaluate the association between genetic polymorphisms of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T with male infertility susceptibility. A total of 392 men including 178 infertile males (102 idiopathic azoospermia and 76 severe oligozoospermia) and 214 healthy controls were recruited. XRCC6 -61C>G and XRCC7 6721G>T genotyping was performed by PCR-RFLP whereas XRCC5 VNTR was performed by PCR. The 2R allele and 2R allele carriers of XRCC5 VNTR polymorphism significantly decreased risk of male infertility. The mutant GG genotypes and carriers of the CG and GG genotypes of XRCC6 -61C>G showed increased risk for the male infertility. Furthermore, the G allele of the XRCC6 -61C>G was correlated with increased susceptibility to male infertility. Likewise, the T allele of the XRCC7 6721G>T polymorphism was associated with increased susceptibility to male infertility in azoospermia. In silico analysis predicted that the presence of tandem repeats in XRCC5 gene prompter can be sequence to bind to more nuclear factors. Also, rs2267437 (C>G) variant was located in a well-conserved region in XRCC6 promoter and this variation might lead to differential allelic expression. The XRCC7 6721G>T gene polymorphism occurred in an acceptor-splicing site, but this polymorphism has no severe modification on XRCC7 mRNA splicing. Our results indicate the association of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T gene polymorphisms with male infertility in Iranian men.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with Male Infertility Risk: Evidences from Case-Control and In Silico Studies

Jahantigh

Colagar

2017

International Journal of Endocrinology

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“…Studies in Chinese and Iranian populations have demonstrated the presence of VNTR alleles ranging from 0 to 3 21-bp tandem repeats (0R, 1R, 2R, and 3R), with individual genotypes of 0R/0R, 1R/0R, 1R/1R, 2R/0R, 2R/1R, 2R/2R, 3R/0R, 3R/1R, and 3R/2R ( 22 , 23 ). Experimental data indicate that the number of VNTR repeats is inversely related to XRCC5 expression, with an increase in the number of VNTR repeats linked to decreased XRCC5 expression ( 27 – 29 ) (Figure 1 A). VNTR polymorphisms in the XRCC5 promoter are associated with sporadic bladder, gastric, and breast cancer ( 30 – 32 ).…”

Section: Introductionmentioning

confidence: 99%

Differences of Variable Number Tandem Repeats in XRCC5 Promoter Are Associated with Increased or Decreased Risk of Breast Cancer in BRCA Gene Mutation Carriers

et al. 2016

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Ku80 is a subunit of the Ku heterodimer that binds to DNA double-strand break ends as part of the non-homologous end joining (NHEJ) pathway. Ku80 is also involved in homologous recombination (HR) via its interaction with BRCA1. Ku80 is encoded by the XRCC5 gene that contains a variable number tandem repeat (VNTR) insertion in its promoter region. Different VNTR genotypes can alter XRCC5 expression and affect Ku80 production, thereby affecting NHEJ and HR pathways. VNTR polymorphism is associated with multiple types of sporadic cancer. In this study, we investigated its potential association with familial breast cancer at the germline level. Using PCR, PAGE, Sanger sequencing, and statistical analyses, we compared VNTR genotypes in the XRCC5 promoter between healthy individuals and three types of familial breast cancer cases: mutated BRCA1 (BRCA1+), mutated BRCA2 (BRCA2+), and wild-type BRCA1/BRCA2 (BRCAx). We observed significant differences of VNTR genotypes between control and BRCA1+ group (P < 0.0001) and BRCA2+ group (P = 0.0042) but not BRCAx group (P = 0.2185), and the differences were significant between control and cancer-affected BRCA1+ cases (P < 0.0001) and BRCA2+ cases (P = 0.0092) but not cancer-affected BRCAx cases (P = 0.4251). Further analysis indicated that 2R/2R (OR = 1.94, 95%CI = 1.26–2.95, P = 0.0096) and 2R/1R (OR = 1.58, 95%CI = 1.11–2.26, P = 0.0388) were associated with increased risk but 1R/1R (OR = 0.55, 95%CI = 0.35–0.84, P = 0.0196) and 1R/0R (OR = 0, 95%CI = 0–0.29, P = 0.0012) were associated with decreased risk in cancer-affected BRCA1+ group; 2R/1R (OR = 1.94, 95%CI = 1.14–3.32, P = 0.0242) was associated with increased risk in cancer-affected BRCA2+ group. No correlation was observed for the altered risk between cancer-affected or -unaffected carriers and between different age of cancer diagnosis in cancer-affected carriers. The frequently observed VNTR association with in BRCA1+ and BRCA2+ breast cancer group indicates that VNTR polymorphism in the XRCC5 promoter is associated with altered risk of breast cancer in BRCA1+ and BRCA2+ carriers.

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“…32 There are a variable number of tandem repeats of a 21-bp polymorphism (VNTR, rs6147172) in the promoter region of XRCC5, which affect gene expression. 33,34 It is well established that fewer tandem repeats is associated with increased levels of XRCC5 messenger RNA. 34 It has been reported that the XRCC6 promoter T-991C (rs5751129) polymorphism is associated with susceptibility to different multifactorial diseases.…”

Section: Introductionmentioning

confidence: 99%

“…33,34 It is well established that fewer tandem repeats is associated with increased levels of XRCC5 messenger RNA. 34 It has been reported that the XRCC6 promoter T-991C (rs5751129) polymorphism is associated with susceptibility to different multifactorial diseases. 29…”

Section: Introductionmentioning

confidence: 99%

Impact of Sodium Arsenite on Chromosomal Aberrations With Respect to Polymorphisms of Detoxification and DNA Repair Genes

2014

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Arsenic compounds can increase production of reactive oxygen species. Reactive oxygen species can induce double-strand breaks in DNA, which is a cause of chromosome aberrations (CAs). This study was conducted to determine the association between arsenic exposure and polymorphisms of genes involved in detoxification (glutathione S-transferase T1 [GSTT1], glutathione S-transferase M1 [GSTM1], glutathione S-transferase O2 [GSTO2], catalase [CAT], and NAD(P)H quinone oxidoreductase1 [NQO1]) as well as nonhomologous end joining DNA repair genes (XRCC4, XRCC5, and XRCC6) with induction of chromosomal aberrations. The participants consisted of 123 healthy males who were genotyped using polymerase chain reaction-based methods. Primary cultures of whole blood were treated with sodium arsenite (NaAsO(2); iAs(III); at final concentration 1 µmol/L), mitomycin C (at final concentration 60 ηg/mL; as positive control), or untreated. For each culture, mitotic index (MI), chromatid breaks (CBs), CAs, and total percentage of aberrant cells were determined. The levels of CB and percentage of aberrant cells were significantly higher in the TT genotype of CAT (C-262T polymorphism) than the CC genotype. The CB value in samples with GSTM1 active genotype was significantly higher than the null genotype. The MI in samples with TT genotype of NQO1 (C609T polymorphism) was significantly higher than MI in samples having CC and CT genotypes. There was no association between MI, CB, CA, and percentage of aberrant cells and polymorphisms of XRCC4, XRCC5, and XRCC6.

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The novel allele (3R) of the VNTR polymorphism in the XRCC5 promoter region dramatically decreases the gene expression

Cited by 10 publications

References 9 publications

XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with Male Infertility Risk: Evidences from Case-Control and In Silico Studies

XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with Male Infertility Risk: Evidences from Case-Control and In Silico Studies

Differences of Variable Number Tandem Repeats in XRCC5 Promoter Are Associated with Increased or Decreased Risk of Breast Cancer in BRCA Gene Mutation Carriers

Impact of Sodium Arsenite on Chromosomal Aberrations With Respect to Polymorphisms of Detoxification and DNA Repair Genes

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