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Article: Gene-environment interactions and preterm birth predictors: A Bayesian network approach.

Elias, Dario E / Santos, Maria R / Campaña, Hebe / Poletta, Fernando A / Heisecke, Silvina L / Gili, Juan A / Ratowiecki, Julia / Cosentino, Viviana R / Uranga, Rocio / Málaga, Diana Rojas / Oliveira Netto, Alice Brinckmann / Brusius-Facchin, Ana Carolina / Saleme, César / Rittler, Mónica / Krupitzki, Hugo B / Camelo, Jorge S Lopez / Gimenez, Lucas G

Genetics and molecular biology

2024 Volume 46, Issue 4, Page(s) e20230090

Abstract: Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify gene-environment interactions associated with spontaneous PTB or its predictors. We carried out a retrospective case-control ... ...

Abstract	Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify gene-environment interactions associated with spontaneous PTB or its predictors. We carried out a retrospective case-control study including parental sociodemographic and obstetric data as well as newborn genetic variants of 69 preterm and 61 at term newborns born at a maternity hospital from Tucumán, Argentina, between 2005 and 2010. A data-driven Bayesian network including the main PTB predictors was created where we identified gene-environment interactions. We used logistic regressions to calculate the odds ratios and confidence intervals of the interactions. From the main PTB predictors (nine exposures and six genetic variants) we identified an interaction between low neighbourhood socioeconomic status and rs2074351 (PON1, genotype GG) variant that was associated with an increased risk of toxoplasmosis (odds ratio 12.51, confidence interval 95%: 1.71 - 91.36). The results of this exploratory study suggest that structural social disparities could influence the PTB risk by increasing the frequency of exposures that potentiate the risk associated with individual characteristics such as genetic traits. Future studies with larger sample sizes are necessary to confirm these findings.
Language	English
Publishing date	2024-01-19
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	1445712-x
ISSN	1678-4685 ; 1415-4757
ISSN (online)	1678-4685
ISSN	1415-4757
DOI	10.1590/1678-4685-GMB-2023-0090
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Article ; Online: Genetic susceptibility for retinopathy of prematurity and its associated comorbidities.

Gimenez, Lucas G / Gili, Juan A / Elias, Darío E / Sagula, Rubén / Comas, Belén / Santos, María R / Campaña, Hebe / Poletta, Fernando A / Heisecke, Silvina L / Ratowiecki, Julia / Cosentino, Viviana R / Uranga, Rocío / Saleme, César / Negri, Mercedes / Rittler, Mónica / Zapata Barrios, Jorge / Krupitzki, Hugo B / López Camelo, Jorge S

Pediatric research

2024

Abstract: Background: Retinopathy of prematurity (ROP) is one of the leading cause of child blindness. Preterm newborns of very low gestational age (GA) and very low birth weight are at the greatest risk. Our objective was to evaluate the role of genetic variants ...

Abstract	Background: Retinopathy of prematurity (ROP) is one of the leading cause of child blindness. Preterm newborns of very low gestational age (GA) and very low birth weight are at the greatest risk. Our objective was to evaluate the role of genetic variants associated with ROP risk and its comorbidities in an Argentinian sample of premature infants. Methods: A sample of 437 preterm infants <33 weeks GA, born at a maternity hospital in Tucumán, Argentina, 2005-2010, was analyzed. Environmental factors, perinatal outcomes, and fourteen single nucleotide polymorphisms associated with ROP were evaluated, comparing ROP with non-ROP newborns. A lasso logistic regression was performed to select variables; then, a conditional logistic regression was used to identify ROP maternal and perinatal risk factors adjusting by maternal and gestational ages, respectively. Results: ROP maternal risk factors were alcohol intake, periodontal infections, and severe stress. Respiratory distress, sepsis, and intracranial hemorrhage were the ROP perinatal risk factors. Markers rs186085 of EPAS1 and rs427832 of AGTR1 were significantly associated with ROP newborns. Conclusion: We identified three maternal and three perinatal risk factors associated with ROP. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP. Impact: Genetic and environmental risk factors associated with ROP and its comorbidities are evaluated in a Latin American population. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP. Three maternal and three perinatal risk factors associated with ROP were also identified. A matrix of significant relationships among genetic markers and comorbidities is presented. Reported data may help develop more effective preventive measures for ROP in the Latin American region.
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-024-03068-9
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Article: Genes, exposures, and interactions on preterm birth risk: an exploratory study in an Argentine population.

Elias, Dario E / Santos, Maria R / Campaña, Hebe / Poletta, Fernando A / Heisecke, Silvina L / Gili, Juan A / Ratowiecki, Julia / Cosentino, Viviana / Uranga, Rocio / Málaga, Diana Rojas / Netto, Alice Brinckmann Oliveira / Brusius-Facchin, Ana Carolina / Saleme, César / Rittler, Mónica / Krupitzki, Hugo B / Camelo, Jorge S Lopez / Gimenez, Lucas G

Journal of community genetics

2022 Volume 13, Issue 6, Page(s) 557–565

Abstract: Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify associations of spontaneous PTB with genetic variants, exposures, and interactions between and within them. We carried out a ... ...

Abstract	Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify associations of spontaneous PTB with genetic variants, exposures, and interactions between and within them. We carried out a retrospective case-control study including parental sociodemographic and obstetric data, and fetal genetic variants. We sequenced the coding and flanking regions of five candidate genes from the placental blood cord of 69 preterm newborns and 61 at term newborns. We identify the characteristics with the greatest predictive power of PTB using penalized regressions, in which we include exposures (E), genetic variants (G), and two-way interactions. Few prenatal visits (< 5) was the main predictor of PTB from 26 G, 35 E, 299 G × G, 564 E × E, and 875 G × E evaluated terms. Within the fetal genetic characteristics, we observed associations of rs4845397 (KCNN3, allele T) variant; G × G interaction between rs12621551 (COL4A3, allele T) and rs73993878 (COL4A3, allele A), which showed sensitivity to anemia; and G × G interaction between rs11680670 (COL4A3, allele T) and rs2074351 (PON1, allele A), which showed sensitivity to vaginal discharge. The results of this exploratory study suggest that social disparities and metabolic pathways linked to uterine relaxation, inflammation/infections, and collagen metabolism would be involved in PTB etiology. Future studies with a larger sample size are necessary to confirm these findings and to analyze a greater number of exposures.
Language	English
Publishing date	2022-08-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2543127-4
ISSN	1868-6001 ; 1868-310X
ISSN (online)	1868-6001
ISSN	1868-310X
DOI	10.1007/s12687-022-00605-z
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Article ; Online: Preterm birth etiological pathways: a Bayesian networks and mediation analysis approach.

Elias, Dario / Campaña, Hebe / Poletta, Fernando A / Heisecke, Silvina L / Gili, Juan A / Ratowiecki, Julia / Pawluk, Mariela / Santos, Maria R / Cosentino, Viviana / Uranga, Rocio / Saleme, Cesar / Rittler, Monica / Krupitzki, Hugo B / Lopez Camelo, Jorge S / Gimenez, Lucas G

Pediatric research

2021 Volume 91, Issue 7, Page(s) 1882–1889

Abstract: Background: The aim of this study was to determine the mediating effect of spontaneous preterm birth (PTB) main predictors that would allow to suggest etiological pathways.: Methods: We carried out a case-control study, including sociodemographic ... ...

Abstract	Background: The aim of this study was to determine the mediating effect of spontaneous preterm birth (PTB) main predictors that would allow to suggest etiological pathways. Methods: We carried out a case-control study, including sociodemographic characteristics, habits, health care, and obstetric data of multiparous women who gave birth at a maternity hospital from Tucumán, Argentina, between 2005 and 2010: 998 women without previous PTB who delivered at term and 562 who delivered preterm. We selected factors with the greatest predictive power using a penalized logistic regression model. A data-driven Bayesian network including the selected factors was created where we identified pathways and performed mediation analyses. Results: We identified three PTB pathways whose natural indirect effect was greater than zero with a 95% confidence interval: maternal age less than 20 years mediated by few prenatal visits, vaginal bleeding in the first trimester mediated by vaginal bleeding in the second trimester, and urinary tract infection mediated by vaginal bleeding in the second trimester. The effect mediated in these pathways showed greater sensitivity to confounders affecting the variables mediator-outcome and exposure-mediator in the same direction. Conclusion: The identified pathways suggest PTB etiological lines related to social disparities and exposure to genitourinary tract infections. Impact: Few prenatal visits (<5) and vaginal bleeding are two of the main predictors for spontaneous preterm birth in the studied population. Few prenatal visits mediates part of the risk associated with maternal age less than 20 years and vaginal bleeding in the second trimester mediates part of the risk associated with vaginal bleeding in the first trimester and with urinary tract infection. Social disparities and exposure to genitourinary tract infections would be etiological lines of spontaneous preterm birth.
MeSH term(s)	Adult ; Bayes Theorem ; Case-Control Studies ; Female ; Humans ; Infant, Newborn ; Mediation Analysis ; Pregnancy ; Premature Birth/epidemiology ; Premature Birth/etiology ; Risk Factors ; Uterine Hemorrhage/complications ; Young Adult
Language	English
Publishing date	2021-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-021-01659-4
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Preterm birth and genitourinary tract infections: assessing gene-environment interaction.

Elias, Dario / Gimenez, Lucas / Poletta, Fernando / Campaña, Hebe / Gili, Juan / Ratowiecki, Julia / Pawluk, Mariela / Rittler, Monica / Santos, Maria R / Uranga, Rocio / Heisecke, Silvina L / Cosentino, Viviana / Saleme, Cesar / Gadow, Enrique / Krupitzki, Hugo / Camelo, Jorge S Lopez

Pediatric research

2020 Volume 90, Issue 3, Page(s) 678–683

Abstract: Background: Preterm birth (PTB) is the leading cause of perinatal morbimortality worldwide. Genetic and environmental factors could raise PTB risk. The aim of this study was to analyze the contribution of the statistical interaction between genes and ... ...

Abstract	Background: Preterm birth (PTB) is the leading cause of perinatal morbimortality worldwide. Genetic and environmental factors could raise PTB risk. The aim of this study was to analyze the contribution of the statistical interaction between genes and vaginal-urinary tract infections (VI-UTI) to the risk of PTB by clinical subtype. Methods: Twenty-four SNPs were genotyped in 18 candidate genes from 352 fetal triads and 106 maternal triads. Statistical interactions were evaluated with conditional logistic regression models based on genotypic transmission/disequilibrium test. Results: In PTB-idiopathic subtype mothers exposed to UTI, fetal SNPs rs11686474 (FSHR), rs4458044 (CRHR1, allele G), rs883319 (KCNN3), and maternal SNP rs1882435 (COL4A3) showed a nominal significant increment in prematurity risk. In preterm premature rupture of membranes (PPROM), fetal SNP rs2277698 (TIMP2) showed a nominal significant risk increment. In mothers exposed to VI, fetal SNP rs5742612 (IGF1) in PTB-PPROM and maternal SNP rs4458044 (CRHR1, allele C) in spontaneous PTB showed nominal significant increment in prematurity risk. Conclusions: Certain maternal and fetal genes linked to infectious/inflammatory and hormonal regulation processes increase prematurity risk according to clinical subtype when mothers are exposed to UTI or VI. These findings may help in the understanding of PTB etiology and PTB prevention. Impact: Preterm birth is a major cause of perinatal morbimortality worldwide and its etiology remains unknown. This work provides evidence on the statistical interaction of six genes with gestational vaginal or urinary infections leading to the occurrence of preterm births. Statistical interactions vary according to infection type, genotype (maternal and fetal), and clinical subtype of prematurity. Certain maternal and fetal genetic variants of genes linked to infectious/inflammatory and hormonal regulation processes would increase the risk of prematurity according to clinical subtype and infection type. Our findings may help in the study of etiology of preterm birth and its prevention.
MeSH term(s)	Gene-Environment Interaction ; Genital Diseases/epidemiology ; Genital Diseases/genetics ; Humans ; Infant, Newborn ; Polymorphism, Single Nucleotide ; Premature Birth ; Risk Factors ; Urinary Tract Infections/epidemiology ; Urinary Tract Infections/genetics
Language	English
Publishing date	2020-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-020-01200-z
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Article: Behavioral symptoms related to cognitive impairment.

Dillon, Carol / Serrano, Cecilia M / Castro, Diego / Leguizamón, Patricio Perez / Heisecke, Silvina L / Taragano, Fernando E

Neuropsychiatric disease and treatment

2013 Volume 9, Page(s) 1443–1455

Abstract: Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. On one hand, behavioral symptoms in patients with mild cognitive impairment (MCI) can indicate an increased risk of progressing to dementia. On the other hand, ...

Abstract	Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. On one hand, behavioral symptoms in patients with mild cognitive impairment (MCI) can indicate an increased risk of progressing to dementia. On the other hand, mild behavioral impairment (MBI) in patients who usually have normal cognition indicates an increased risk of developing dementia. Whatever the cause, all dementias carry a high rate of NPI. These symptoms can be observed at any stage of the disease, may fluctuate over its course, are a leading cause of stress and overload for caregivers, and increase rates of hospitalization and early institutionalization for patients with dementia. The clinician should be able to promptly recognize NPI through the use of instruments capable of measuring their frequency and severity to support diagnosis, and to help monitor the treatment of behavioral symptoms. The aims of this review are to describe and update the construct 'MBI' and to revise the reported NPS related to prodromal stages of dementia (MCI and MBI) and dementia stages of Alzheimer's disease and frontotemporal lobar degeneration.
Language	English
Publishing date	2013-09-19
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2186503-6
ISSN	1178-2021 ; 1176-6328
ISSN (online)	1178-2021
ISSN	1176-6328
DOI	10.2147/NDT.S47133
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Article ; Online: Risk of Conversion to Dementia in a Mild Behavioral Impairment Group Compared to a Psychiatric Group and to a Mild Cognitive Impairment Group.

Taragano, Fernando E / Allegri, Ricardo F / Heisecke, Silvina L / Martelli, María I / Feldman, Mónica L / Sánchez, Viviana / García, Virginia A / Tufro, Graciela / Castro, Diego M / Leguizamón, Patricio Perez / Guelar, Verónica / Ruotolo, Eva / Zegarra, Cecilia / Dillon, Carol

Journal of Alzheimer's disease : JAD

2018 Volume 62, Issue 1, Page(s) 227–238

Abstract: Background: There is insufficient available information on behavioral changes in the absence of cognitive impairment as factors increasing the risk of conversion to dementia.: Objective: To observe and analyze patients with mild behavioral impairment ...

Abstract	Background: There is insufficient available information on behavioral changes in the absence of cognitive impairment as factors increasing the risk of conversion to dementia. Objective: To observe and analyze patients with mild behavioral impairment (MBI), mild cognitive impairment (MCI), and a psychiatry group (PG) to compare the risk of progression to dementia. Methods: From 677 initially assessed ≥60-year-old patients, a series of 348 patients was studied for a five-year period until censoring or conversion to dementia: 96 with MBI, 87 with MCI, and 165 with general psychiatry disorders, including 4 subgroups: Anxiety, Depression, Psychosis and Others. All patients were assessed with clinical, psychiatric, neurological, neuropsychological, and neuroimaging studies. Results: From 348 patients, 126 evolved to dementia (36.2%). Conversion was significantly higher in MBI (71.5%), followed by the MCI-MBI overlap (59.6%) and MCI (37.8%) groups, compared to PG (13.9%) (Log-rank p < 0.001). MCI patients mostly converted to Alzheimer's dementia, while MBI converted to frontotemporal dementia and Lewy body dementia. Patients in PG converted to Lewy body dementia and frontotemporal dementia. Conclusion: Conversion to dementia is significantly higher in patients with neuropsychiatric symptoms. The MBI concept generates a new milestone in the refining of diagnosis of neurodegenerative diseases and the possibility of creating neuropsychiatric profiles. Its earlier identification will allow new possibilities for therapeutic intervention.
MeSH term(s)	Aged ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/drug therapy ; Cognitive Dysfunction/epidemiology ; Dementia/diagnostic imaging ; Dementia/drug therapy ; Dementia/epidemiology ; Disease Progression ; Female ; Humans ; Kaplan-Meier Estimate ; Longitudinal Studies ; Male ; Mental Disorders/diagnostic imaging ; Mental Disorders/drug therapy ; Mental Disorders/epidemiology ; Middle Aged ; Prospective Studies ; Risk
Language	English
Publishing date	2018-02-10
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-170632
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Article: Una encuesta sobre biomarcadores y diagnóstico precoz de la enfermedad de Alzheimer.

Taragano, Fernando E / Castro, Diego M / Serrano, Cecilia M / Heisecke, Silvina L / Pérez Leguizamón, Patricio / Loñ, Leandro / Dillon, Carol

Medicina

2015 Volume 75, Issue 5, Page(s) 282–288

Abstract: Given the potential use of biomarkers in the diagnosis of Alzheimer's disease (AD) in early stages, new ethical and communication dilemmas appear in everyday clinical practice. The aim of this study was to know the opinion of health professionals (HP) ... ...

Title translation	A survey on biomarkers and early diagnosis in Alzheimer's disease.
Abstract	Given the potential use of biomarkers in the diagnosis of Alzheimer's disease (AD) in early stages, new ethical and communication dilemmas appear in everyday clinical practice. The aim of this study was to know the opinion of health professionals (HP) and general public (GP) on the implementation of early diagnostic techniques in AD and the use of biomarkers for this purpose. A survey with multiple choice answers was elaborated in two versions: one for HP and the other for GP. Respondents were invited to participate through a system of mass mailing e-mail; e-mail addresses were collected from CEMIC database. A total of 1503 answers were analyzed: 807 HP and 696 GP. Most respondents, 84.7%, preferred the option of early diagnosis of AD even knowing the lack of curative treatment. Forty five percent of GP and 26.8% of HP replied that there is no ethical dilemma in the use of biomarkers and that no communication or ethical dilemma is generated to physicians when informing the diagnosis of the disease. The HP group showed more divergence in the views than the GP group. These results may indicate a change in the physician-patient relationship, showing the GP group with an active and supportive position towards the use of biomarkers for early diagnosis of AD.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/prevention & control ; Bioethical Issues ; Biomarkers ; Early Diagnosis ; Genetic Markers ; Health Personnel/ethics ; Humans ; Physician-Patient Relations/ethics ; Public Opinion ; Surveys and Questionnaires
Chemical Substances	Biomarkers ; Genetic Markers
Language	Spanish
Publishing date	2015
Publishing country	Argentina
Document type	English Abstract ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	411586-7
ISSN	1669-9106 ; 0025-7680 ; 0325-951X
ISSN (online)	1669-9106
ISSN	0025-7680 ; 0325-951X
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