The functional polymorphism rs73598374:G&gt;A (p.Asp8Asn) of the ADA gene is associated with telomerase activity and leukocyte telomere length

Concetti, Fabio; Carpi, Francesco M.; Nabissi, Massimo; Picciolini, Matteo; Santoni, Giorgio; Napolioni, Valerio

doi:10.1038/ejhg.2014.102

Cited by 6 publications

(6 citation statements)

References 15 publications

(26 reference statements)

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“…We previously found that shortened leukocyte telomere length significantly contributes to increased risk of GCA [10]. In humans, various genetic variations have been identified to be associated with leukocyte telomere length via GWAS [20][21][22][23][24][25][26][27][28][29] and most of these polymorphisms have been proved to confer cancer susceptibility. In the current study, we, for the first time, systematically evaluate the involvement of these telomere length-related genetic variations in GCA development.…”

Section: Discussionmentioning

confidence: 99%

“…Telomeres length is a heritable trait, with heritability ranging from 44 to 80% and regulated by multiple genes [18,19]. Several genome-wide association studies (GWAS) and candidate gene studies identified dozens of single-nucleotide polymorphisms (SNPs) associated with leucocyte telomere length in different ethnic populations [20][21][22][23][24][25][26][27][28][29]. Intriguingly, multiple telomere length-related SNPs confer risk of different malignancies, such as prostate cancer, ovarian cancer, leukemia, colorectal cancer, glioma, and pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

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Genetic variations associated with telomere length confer risk of gastric cardia adenocarcinoma

et al. 2019

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Background Aberrant telomere lengthening is a critical feature of malignant cells. Short leukocyte telomere length (LTL) confers elevated risk of gastric cardia adenocarcinoma (GCA). Multiple genome-wide association studies (GWAS) identified various single-nucleotide polymorphisms (SNPs) associated with LTL in different ethnic populations. However, it remains largely unexplored how these genetic variants are involved in GCA susceptibility. Methods We systematically screened GWAS-identified candidate SNPs and tested the impact of 30 polymorphisms in genes associated with interindividual LTL variation on GCA using two-stage case-control comparisons consisting of 1024 GCA patients and 1118 controls. Results We observed that CXCR4 rs6430612, TERT rs10069690, and rs2853676 as well as VPS34 rs2162440 are significantly associated with GCA development. A 0.64-fold decreased risk of GCA is associated with the CXCR4 rs6430612 CT genotype compared with the CC genotype (P = 0.002). On the contrary, the TERT rs10069690 TT genotype carriers had a 1.83-fold increased risk to develop GCA compared to the CC genotype carriers (P = 5.8×10 −6 ). We also detected a 2.17-fold increased OR for GCA that was associated with the TERT rs2853676 TT genotype (P = 2.6×10 −6 ). In addition, the odds of having the VPS34 rs2162440 GA genotype in GCA patients were 1.35 compared with the GG genotype (P = 0.002). In stratified analyses, the association between TERT rs10069690 polymorphism and GCA was more pronounced in nonsmokers (P interaction = 9.7 × 10 −5 ) and nondrinkers (P interaction = 4.6 × 10 −5 ). Conclusions Our results highlight the importance of both LTL and LTL-related genetic variants to GCA predisposition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic variations associated with telomere length confer risk of gastric cardia adenocarcinoma

et al. 2019

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“…The heritability estimates of human telomere length are 44%~80%, suggesting the key role of genetic factors in controlling telomere length [26,27]. Several quantitative trait linkage (QTL) GWAS and candidate gene QTL studies have mapped various SNPs correlated to leucocyte telomere length [28][29][30][31][32][33][34][35][36][37]. Several telomere length-related SNPs have been previously found to confer susceptibility of cancers including ESCC.…”

Section: Ivyspringmentioning

confidence: 99%

Identification of Leukocyte telomere length-related genetic variants contributing to predisposition of Esophageal Squamous Cell Carcinoma

Song²,

Xu³

et al. 2020

J. Cancer

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Background: Cancers may arise from cells with dysregulated telomeric functions due to shorten telomere length. We and others previously found that short leukocyte telomere length was associated with markedly evaluated risk of esophageal squamous cell carcinoma (ESCC). Hence, we hypothesized that single nucleotide polymorphisms (SNPs) associated with shorter telomere length may contribute to ESCC predisposition. Methods: We systematically evaluated association between seven candidate seven SNPs (CXCR4 rs6430612, TERT rs13172201, TERT rs10069690, TERT rs2853676, TERT rs451360, OBFC1 rs4387287, and VPS34 rs2162440) and ESCC risk in two case-control sets consisting of 1588 ESCC cases and 1600 controls. Logistic regression models were utilized to estimate associations between SNPs and ESCC susceptibility and odds ratios (ORs) and their 95% confidence intervals (95% CIs) were computed. Results: We firstly identified three SNPs (rs6430612, rs13172201 and rs4387287) which are significantly associated with telomere length in Chinese populations (all P<0.05). Importantly, CXCR4 rs6430612 and OBFC1 rs4387287 polymorphisms significantly confer reduced risk of ESCC (P=1.7×10-7 and P=3.9×10-5). On the contrary, we observed an evidently increased risk for ESCC development associated with TERT rs13172201 genetic variant (P=2.2×10-4). Conclusions: In summary, rs6430612, rs13172201 and rs4387287 might be key genetic components in complicated regulation of telomere length and contributing to ESCC predisposition. Our results elucidate the prevalent involvement of genetic variants in telomere biology and further provide pathogenic insights into the role of telomeres in cancer development.

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“…Adenosine deaminase (ADA), encoded by the ADA gene (gene map locus 20q13.11), is an enzyme that catalyzes irreversible deamination of adenosine to inosine and has a crucial role in regulating extracellular and intracellular adenosine concentration (Franco et al, 2007a;2007b;Concetti et al, 2015). ADA is widely distributed in most mammalian tissues, but the highest activity is observed in lymphoid and fatty tissues (Niedzwicki and Abernethy, 1991;Husseini et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Research Article Association of <i>G22A</i> polymorphism of the adenosine deaminase (<i>ADA</i>) gene with biochemical characteristics in type 2 diabetic Palestinians

Ereqat¹,

Qrea²,

Nasereddin³

2018

Genet. Mol. Res.

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The adenosine deaminase G22A polymorphism (20q.11.33) affects the level of adenosine deaminase (ADA) expression, which plays an important role in the regulation of intracellular and extracellular concentrations of adenosine. Recent studies reported greater ADA activity in diabetic patients and showed the role of ADA in the modulation of insulin activity and glucose homeostasis. We investigated whether the G22A polymorphism of the ADA gene is associated with type 2 diabetes mellitus (T2DM) in the Palestinian population and assessed the relationship between the G22A variant and fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and lipid profile among T2DM patients. A total of 231 individuals with T2DM and a control sample of 101 non-diabetic participants were randomly selected from those who were attending United Nations Relief and Works Agency (UNRWA) clinics for treatment and/or follow up. Genomic DNA was extracted from peripheral blood samples and PCR-RFLP was performed to identify the TaqI polymorphism G22A of the ADA gene. No significant differences were observed in the genotype and allele frequencies between T2DM patients and the control group. Yet, ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 17 (4): gmr18111 S. Ereqat, L. Qrea, A. Nasereddin 2 among diabetic patients, the GG genotype was significantly associated with higher FPG and HbA1c when compared to the GA+AA genotype but had no influence on blood pressure, BMI or other metabolic parameters. In conclusion, we confirm that the GG genotype of the ADA gene is associated with poor glycemic control in T2DM Palestinians and points to the association of the G22A variant with decreased activity of the ADA enzyme, which is of paramount importance in the pathophysiology of T2DM.

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The functional polymorphism rs73598374:G>A (p.Asp8Asn) of the ADA gene is associated with telomerase activity and leukocyte telomere length

Cited by 6 publications

References 15 publications

Genetic variations associated with telomere length confer risk of gastric cardia adenocarcinoma

Genetic variations associated with telomere length confer risk of gastric cardia adenocarcinoma

Identification of Leukocyte telomere length-related genetic variants contributing to predisposition of Esophageal Squamous Cell Carcinoma

Research Article Association of <i>G22A</i> polymorphism of the adenosine deaminase (<i>ADA</i>) gene with biochemical characteristics in type 2 diabetic Palestinians

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