Paradoxical role of C1561T glutamate carboxypeptidase II (GCPII) genetic polymorphism in altering disease susceptibility

Divyya, Shree; Naushad, Shaik Mohammad; Addlagatta, A.; Murthy, Pooja; Reddy, C. R. R. M.; Digumarti, Raghunadha Rao; Gottumukkala, Suryanarayana Raju; Kumar, Ajit; Rammurti, S.; Kutala, Vijay Kumar

doi:10.1016/j.gene.2012.01.055

Cited by 17 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When the prevalence of the GCPII C1561T gene polymorphism among South Indian Tamil population was determined, no individuals with the homozygous mutant "TT" genotype were found among the studied population. Similar kind of result was also observed among the Netherlands and Indian population [4,[19][20][21]. In our study, we have observed deviations from the Hardy-Weinberg law of population genetics for GCPII C1561T polymorphism among the study subjects.…”

Section: Discussionsupporting

confidence: 90%

Prevalence of Glutamate Carboxypeptidase Ii C1561t, Reduced Folate Carrier 1 A80g, and Methionine Synthase A2756g Gene Polymorphisms in Patients With Type 2 Diabetes Mellitus Among South Indians

Nithya¹,

Angeline²,

As³

et al. 2019

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Objective: Glutamate carboxypeptidase II (GCPII), reduced folate carrier 1 (RFC1), and methionine synthase (MTR) genes involved in the folate metabolic pathway may play a key role in the pathogenesis of diabetes and its complications. The present study aimed to investigate the prevalence of genetic polymorphisms of GCPII C1561T, RFC1 A80G, and MTR A2756G in individuals with type 2 diabetes mellitus (T2DM) among South Indians. Methods: The study subjects consisted of 100 healthy individuals and 200 patients with T2DM. Genetic polymorphisms (GCPII C1561T, RFCI A80G, and MTR A2756G) in the folate metabolic pathway were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis was performed to test the level of significance. Results: With regard to GCPII C1561T and MTR A2756G gene polymorphisms, significant differences were not found when diabetic patients (with and without complications) and controls were compared according to different statistical models (dominant, recessive, and overdominant) p>0.05. A case–control genetic association analysis of RFC1 A80G gene polymorphism has shown that there was 3.7-fold increased risk for patients without complications and 4.9-fold increased risk for diabetic patients with complications. Conclusions: Our findings suggest that the GCPII C1561T and MTR A2756G gene polymorphisms were not significantly associated with diabetes and its complications. Whereas, the RFCI A80G gene polymorphism involved in folate metabolism confers increased risk for diabetes and its complications in South Indian population.

show abstract

Section: Discussionsupporting

confidence: 90%

Prevalence of Glutamate Carboxypeptidase Ii C1561t, Reduced Folate Carrier 1 A80g, and Methionine Synthase A2756g Gene Polymorphisms in Patients With Type 2 Diabetes Mellitus Among South Indians

Nithya¹,

Angeline²,

As³

et al. 2019

Asian J Pharm Clin Res

View full text Add to dashboard Cite

show abstract

“…Although C1561T-GCPII variation did not show a significant difference for blood folate and Hcy levels by adenomatous polyp phenotype in the present study, a number of other reports suggest C1561T-GCPII variation affects folate metabolism and linking it to disease. Divyya et al (2012) reported that C1561T-GCPII variation was associated with risk for coronary artery disease and miscarriage, but only had an influence on folate metabolism in subjects taking the lowest tertile of dietary folate. The difference in plasma folate level by 1561T allele was not evident in the subjects with higher dietary folate intake.…”

Section: Discussionmentioning

confidence: 99%

“…The high intake of folate in the current subjects, possibly due to discretionary use of PteGlu, would not require substantial GCPII activity since the synthetic PteGlu is already in monoglutamate form. In fact, the abundance of dietary PteGlu may nullify the influence derived from C1561T-GCPII on folate metabolism (Divyya et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…GCPII and its genetic variants are known to be associated with folate nutritional status and disease 1 susceptibility, as this is a critical locus for the absorption mechanism of methylfolate (Devlin et al, 2000). One particular mutation of this gene, C1561T in which histidine 475 is changed to tyrosine (rs61886492, H475Y), has been reported to be associated with risk for breast and prostate cancer, coronary artery disease and miscarriage (Divyya et al, 2012;Vijaya Lakshmi et al, 2013). This genetic variant may lead to a reduction in GCPII activity, and hence to a lower blood folate concentration and higher homocysteine (Hcy), potentially implicating this polymorphism in the pathoaetiology of these disorders (Devlin et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Variation in Glutamate Carboxypeptidase II and Interaction with Dietary Natural Vitamin C May Predict Risk for Adenomatous Polyp Occurrence

Choi¹,

Yates²,

Martin³

et al. 2015

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: The C1561T variant of the glutamate carboxypeptidase II (GCPII) gene is critical for natural methylfolylpolyglutamte (methylfolate) absorption, and has been associated with perturbations in folate metabolism and disease susceptibility. However, little is known on C1561T-GCPII as a risk factor for colorectal cancer. Therefore, this study examined whether C1561T-GCPII influences folate metabolism and adenomatous polyp occurrence. Materials and Methods: 164 controls and 38 adenomatous polyp cases were analysed to determine blood folate and plasma homocysteine (Hcy) level, dietary intake of natural methylfolate, synthetic pteroylglutamic acid (PteGlu), vitamin C and C1561T-GCPII genotype. Results: In controls and cases, 7.3 and 18.4 percent of subjects respectively, were found to have the CT genotype, increasing the risk for adenomatous polyp occurrence 2.86 times (95% CI:1.37-8.0, p=0.035). Total dietary folate, methylfolate and PteGlu intake and the level of erythrocyte folate and plasma Hcy did not predict the occurrence of an adenomatous polyp. However, dietary natural vitamin C intake was associated with adenomatous polyp risk within C1561T-GCPII CT genotype subjects (p=0.037). Conclusions: The findings suggest that C1561T-GCPII variation may be associated with risk for adenomatous polyp, and vitamin C may modify risk by interacting with the variant gene, its expression product and/or folate substrates.

show abstract

“…The GCPII D191V mutation promotes SOD3 hypermethylation and is associated with an increased risk of breast cancer [167 177]. Additionally, the GCPII H475Y variant is associated with decreased SOD3 methylation and decreased risk of breast and prostate cancer [167 178]. These studies imply an interplay between EcSOD and GCPII variants associated with cancer risk via changes in the folate cycle and DNA methylation status of EcSOD.…”

Section: Deregulation Of Ecsod In Cancersmentioning

confidence: 99%

Extracellular superoxide dismutase and its role in cancer

Griess

Tom

Domann

et al. 2017

Free Radical Biology and Medicine

144

124

View full text Add to dashboard Cite

Reactive oxygen species (ROS) are increasingly recognized as critical determinants of cellular signaling and a strict balance of ROS levels must be maintained to ensure proper cellular function and survival. Notably, ROS is increased in cancer cells. The superoxide dismutase family plays an essential physiological role in mitigating deleterious effects of ROS. Due to the compartmentalization of ROS signaling, EcSOD, the only superoxide dismutase in the extracellular space, has unique characteristics and functions in cellular signal transduction. In comparison to the other two intracellular SODs, EcSOD is a relatively new comer in terms of its tumor suppressive role in cancer and the mechanisms involved are less well understood. Nevertheless, the degree of differential expression of this extracellular antioxidant in cancer versus normal cells/tissues is more pronounced and prevalent than the other SODs. A significant association of low EcSOD expression with reduced cancer patient survival further suggests that loss of extracellular redox regulation promotes a conducive microenvironment that favors cancer progression. The vast array of mechanisms reported in mediating deregulation of EcSOD expression, function, and cellular distribution also supports that loss of this extracellular antioxidant provides a selective advantage to cancer cells. Moreover, overexpression of EcSOD inhibits tumor growth and metastasis, indicating a role as a tumor suppressor. This review focuses on the current understanding of the mechanisms of deregulation and tumor suppressive function of EcSOD in cancer.

show abstract

Paradoxical role of C1561T glutamate carboxypeptidase II (GCPII) genetic polymorphism in altering disease susceptibility

Cited by 17 publications

References 51 publications

Prevalence of Glutamate Carboxypeptidase Ii C1561t, Reduced Folate Carrier 1 A80g, and Methionine Synthase A2756g Gene Polymorphisms in Patients With Type 2 Diabetes Mellitus Among South Indians

Prevalence of Glutamate Carboxypeptidase Ii C1561t, Reduced Folate Carrier 1 A80g, and Methionine Synthase A2756g Gene Polymorphisms in Patients With Type 2 Diabetes Mellitus Among South Indians

Genetic Variation in Glutamate Carboxypeptidase II and Interaction with Dietary Natural Vitamin C May Predict Risk for Adenomatous Polyp Occurrence

Extracellular superoxide dismutase and its role in cancer

Contact Info

Product

Resources

About