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Dive into the research topics where Patricia Cuenca is active.

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Featured researches published by Patricia Cuenca.


Clinical and Experimental Medicine | 2005

Association of interleukin-1B and interleukin-1RN polymorphisms with gastric cancer in a high-risk population of Costa Rica.

Warner Alpízar-Alpízar; Guillermo I. Perez-Perez; Clas Une; Patricia Cuenca; Rafaela Sierra

Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1β (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/– had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34–10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09–7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed.


Human Molecular Genetics | 2012

Somatic instability of the expanded CTG triplet repeat in myotonic dystrophy type 1 is a heritable quantitative trait and modifier of disease severity

Fernando Morales; Jillian M. Couto; Catherine F. Higham; Grant Hogg; Patricia Cuenca; Claudia Braida; Richard H. Wilson; Berit Adam; Gerardo del Valle; Roberto Brian; Mauricio Sittenfeld; Tetsuo Ashizawa; Alison Wilcox; Douglas Wilcox; Darren G. Monckton

Deciphering the contribution of genetic instability in somatic cells is critical to our understanding of many human disorders. Myotonic dystrophy type 1 (DM1) is one such disorder that is caused by the expansion of a CTG repeat that shows extremely high levels of somatic instability. This somatic instability has compromised attempts to measure intergenerational repeat dynamics and infer genotype-phenotype relationships. Using single-molecule PCR, we have characterized more than 17 000 de novo somatic mutations from a large cohort of DM1 patients. These data reveal that the estimated progenitor allele length is the major modifier of age of onset. We find no evidence for a threshold above which repeat length does not contribute toward age at onset, suggesting pathogenesis is not constrained to a simple molecular switch such as nuclear retention of the DMPK transcript or haploinsufficiency for DMPK and/or SIX5. Importantly, we also show that age at onset is further modified by the level of somatic instability; patients in whom the repeat expands more rapidly, develop the symptoms earlier. These data establish a primary role for somatic instability in DM1 severity, further highlighting it as a therapeutic target. In addition, we show that the level of instability is highly heritable, implying a role for individual-specific trans-acting genetic modifiers. Identifying these trans-acting genetic modifiers will facilitate the formulation of novel therapies that curtail the accumulation of somatic expansions and may provide clues to the role these factors play in the development of cancer, aging and inherited disease in the general population.


DNA Repair | 2016

A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients.

Fernando Morales; Melissa Vásquez; Carolina Santamaría; Patricia Cuenca; Eyleen Corrales; Darren G. Monckton

Somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 is age-dependent, tissue-specific and expansion-biased, contributing toward the tissue-specificity and progressive nature of the symptoms. Previously, using regression modelling of repeat instability we showed that variation in the rate of somatic expansion in blood DNA contributes toward variation in age of onset, directly implicating somatic expansion in the disease pathway. Here, we confirm these results using a larger more genetically homogenous Costa Rican DM1 cohort (p<0.001). Interestingly, we also provide evidence that supports subtle sex-dependent differences in repeat length-dependent age at onset and somatic mutational dynamics. Previously, we demonstrated that variation in the rate of somatic expansion was a heritable quantitative trait. Given the important role that DNA mismatch repair genes play in mediating expansions in mouse models, we tested for modifier gene effects with 13 DNA mismatch gene polymorphisms (one each in MSH2, PMS2, MSH6 and MLH1; and nine in MSH3). After correcting for allele length and age effects, we identified three polymorphisms in MSH3 that were associated with variation in somatic instability: Rs26279 (p=0.003); Rs1677658 (p=0.009); and Rs10168 (p=0.031). However, only the association with Rs26279 remained significant after multiple testing correction. Although we revealed a statistically significant association between Rs26279 and somatic instability, we did not detect an association with the age at onset. Individuals with the A/A genotype for Rs26279 tended to show a greater propensity to expand the CTG repeat than other genotypes. Interestingly, this SNP results in an amino acid change in the critical ATPase domain of MSH3 and is potentially functionally dimorphic. These data suggest that MSH3 is a key player in generating somatic variation in DM1 patients and further highlight MSH3 as a potential therapeutic target.


European Journal of Human Genetics | 2015

Parental age effects, but no evidence for an intrauterine effect in the transmission of myotonic dystrophy type 1

Fernando Morales; Melissa Vásquez; Patricia Cuenca; Domingo Campos; Carolina Santamaría; Gerardo del Valle; Roberto Brian; Mauricio Sittenfeld; Darren G. Monckton

Myotonic dystrophy type 1 (DM1) is caused by the expansion of an unstable CTG repeat (g.17294_17296(45_1000)) with more repeats associated with increased disease severity and reduced age at onset. Expanded disease-associated alleles are highly unstable in both the germline and soma. Germline instability is expansion biased, providing a molecular explanation for anticipation. Somatic instability is expansion biased, size- and age-dependent, features that have compromised genotype–phenotype correlations and intergenerational studies. We corrected these confounding factors by estimating the progenitor allele length in 54 father–offspring and 52 mother–offspring pairs in Costa Rican DM1 families. Not surprisingly, we found major parental allele length effects on the size of the allele transmitted, the magnitude of the intergenerational length change, the age at onset in the next generation and the degree of anticipation in both male and female transmissions. We also detected, for the first time, an age-of-parent effect for both male and female transmission. Interestingly, we found no evidence for an intrauterine effect in the transmission of congenital DM1, suggesting previous reports may have been an artefact of age-dependent somatic instability and sampling bias. These data provide new insights into the germline dynamics of the CTG repeat and opportunities for providing additional advice and more accurate risk assessments to prospective parents in DM1 families.


Human Mutation | 2016

Identification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patients

Rebeca Vindas-Smith; Michele Fiore; Melissa Vásquez; Patricia Cuenca; Gerardo Del Valle; Laura Lagostena; Héctor Gaitán-Peñas; Raúl Estévez; Michael Pusch; Fernando Morales

Mutations in the gene coding for the skeletal muscle Cl− channel (CLCN1) lead to dominant or recessive myotonia. Here, we identified and characterized CLCN1 mutations in Costa Rican patients, who had been clinically diagnosed with myotonic dystrophy type 1 but who were negative for DM1 mutations. CLCN1 mutations c.501C>G, p.F167L and c.1235A>C, p.Q412P appeared to have recessive inheritance but patients had atypical clinical phenotypes; c.313C>T, p.R105C was found in combination with c.501C>G, p.F167L in an apparently recessive family and the c.461A>G, p.Q154R variant was associated with a less clear clinical picture. In Xenopus oocytes, none of the mutations exhibited alterations of fast or slow gating parameters or single channel conductance, and mutations p.R105C, p.Q154R, and p.F167L were indistinguishable from wild‐type (WT). p.Q412P displayed a dramatically reduced current density, surface expression and exerted no dominant negative effect in the context of the homodimeric channel. Fluorescently tagged constructs revealed that p.Q412P is expressed inefficiently. Our study confirms p.F167L and p.R105C as myotonia mutations in the Costa Rican population, whereas p.Q154R may be a benign variant. p.Q412P most likely induces a severe folding defect, explaining the lack of dominance in patients and expression systems, but has WT properties once expressed in the plasma membrane.


Psychiatry Research-neuroimaging | 2016

Candidate gene study reveals DRD1 and DRD2 as putative interacting risk factors for youth depression

Eyleen Corrales; Arcadi Navarro; Patricia Cuenca; Domingo Campos

Alterations in the monoaminergic neurotransmission systems are suspected to be involved in the etiology of neuropsychiatric disorders, including depression. The role of these pathways in the risk of developing depressive symptoms during childhood or adolescence is still not completely clear. This study sought to identify putative genetic factors in genes of serotonergic and dopaminergic systems modulating the level of manifestation of depressive symptoms in children and adolescents. We analyzed 170 single nucleotide polymorphisms (SNPs) in 21 candidate dopaminergic and serotonergic genes in a non-clinical sample of 410 Costa Rican participants of ages between 7 and 18 years, assessing the severity of depressive symptoms through the Child Depression Inventory (CDI). Genotypic and haplotypic associations, as well as epistatic effects, were examined. A significant interaction effect was detected between rs1039089 in conjunction with rs877138 located upstream of the dopamine D1 receptor (DRD1) and the dopamine D2 receptor (DRD2) genes respectively, although no evidence was found for any single variant or haplotype related to a differential liability. This newly described genetic interaction among putative regulatory regions of dopamine receptors could affect the level of manifestation of depressive symptoms through an imbalance of D1-D2 heteromers and modulation of cognitive processes.


Revista De Biologia Tropical | 2002

Daño del ADN en trabajadoras bananeras expuestas a plaguicidas en Limón, Costa Rica

Vanessa Ramírez; Patricia Cuenca


Revista De Biologia Tropical | 2014

Polimorfismos en los genes de desintoxicación CYP1A1, CYP2E1, GSTT1 y GSTM1 en la susceptibilidad al cáncer gástrico

Auxiliadora González; Vanessa Ramírez; Patricia Cuenca; Rafaela Sierra


World Journal of Gastroenterology | 2008

Relation of atrophic gastritis with Helicobacter pylori -CagA + and interleukin-1 gene polymorphisms

Rafaela Sierra; Clas Une; Vanessa Ramírez; Warner Alpízar-Alpízar; María Isabel González; José A. Ramírez; Antoine de Mascarel; Patricia Cuenca; Guillermo I. Perez-Perez; Francis Mégraud


Revista De Biologia Tropical | 2004

Polymorphisms in detoxification genes CYP1A1, CYP2E1, GSTT1 and GSTM1 in gastric cancer susceptibility.

Auxiliadora González; Vanessa Ramírez; Patricia Cuenca; Rafaela Sierra

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Rafaela Sierra

University of Costa Rica

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Clas Une

University of Costa Rica

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Tetsuo Ashizawa

Houston Methodist Hospital

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