Publications by authors named "Blanca Estela Del Rio-Navarro"

56 Publications

Global Asthma Network Phase I study in Mexico: prevalence of asthma symptoms, risk factors and altitude associations-a cross-sectional study.

BMJ Open Respir Res 2020 12;7(1)

Allergy and Immunology, Hospital General de Matamoros, Matamoros, Mexico.

Background: Global Asthma Network (GAN) was established in 2012 as a development to the International Study of Asthma and Allergies in Childhood to improve asthma care globally.

Objective: To survey asthma, allergic rhinitis and atopic dermatitis in primary and secondary school children and to investigate and evaluate its prevalence, severity, management and risk factors in Mexico.

Methods: GAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016-2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by parents of 6-7-year-old primary school pupils (school children) and by 13-14-year-old adolescents.

Results: A total of 35 780 school children and 41 399 adolescents participated. Wheezing ever prevalence was 26.2% (95% CI 25.8% to 26.7%) in school children and 23.9% (95% CI 23.4% to 24.3%) in adolescents. The corresponding frequencies for current wheeze were 10.2% (95% CI 9.9% to 10.5%) and 11.6% (95% CI 11.2% to 11.9%). In school children, the risk factors for current wheeze were rhinitis (OR 4.484; 95% CI 3.915% to 5.134%) and rash symptoms (OR 1.735; 95% CI 1.461% to 2.059%). For adolescents, rhinitis symptoms (OR 3.492; 95% CI 3.188% to 3.825%) and allergic rhinitis diagnosis (OR 2.144; 95% CI 1.787% to 2.572%) were the most significant. For both groups, there was a negative relation with centres' sea level altitude higher than 1500 m above mean sea level (p<0.005).

Conclusions: The most important risk factors for asthma symptoms in both age groups were the presence of rhinitis and rash symptoms or diagnosis. On the other hand, sea level altitude higher than 1500 metres was a protective factor.
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http://dx.doi.org/10.1136/bmjresp-2020-000658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713197PMC
December 2020

The burden of asthma in an inner-city area: A historical review 10 years after Isaac.

World Allergy Organ J 2020 Jan 8;13(1):100092. Epub 2020 Jan 8.

Unit of Clinical Research, Cartagena and Department of Paediatrics, University of Murcia, Murcia, Spain.

Background: According to the International Study of Asthma and Allergies in Childhood (ISAAC) methodology, in 2003, the prevalence of asthma symptoms in children 6-7 years old and adolescents 13-14 years old was 11.6% and 13.7%, respectively. Since then, the number of asthma cases has increased worldwide. The study was conducted in several districts in northern Mexico City to evaluate the prevalence of asthma in these age groups and examine possible risk factors. The data were compared to the 2003 results from the same area.

Methods: This was a comparative cross-sectional study following the official Global Asthma Network (GAN) methodology. The parents or guardians of participants completed a questionnaire that explored demographics, asthma symptoms, diagnoses, and possible risk factors. Central tendency measurements were determined for statistical analysis and chi-squared distribution for possible risk factors.

Results: A total of 2515 children aged 6-7 years and 3375 adolescents aged 13-14 years participated in the study. Compared to the ISAAC results, we found a greater prevalence of wheezing in both children (at some time in life, 19.2% vs. 27.1%; over the last year, 6.8% vs. 10.6%) and adolescents (at some time in life, 16.9% vs. 19.7%), and for children with an asthma diagnosis (4.5% vs. 5.1%). For both groups, the most common risk factor associated with wheezing was the presence of rhinitis symptoms.

Conclusions: Asthma symptoms are highly prevalent in Mexico City, occurring in almost 20% of adolescents. Compared to a decade ago, there was a 7.9% increase in the prevalence of asthma symptoms in children. Almost half of the children and adolescents presenting with symptoms had experienced more than four episodes per year. However, less than 50% of children and adolescents with asthma symptoms had been diagnosed with this disorder, suggesting under-diagnosis.
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http://dx.doi.org/10.1016/j.waojou.2019.100092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953772PMC
January 2020

Cost-effectiveness analysis of OM-85 vs placebo in the prevention of acute respiratory tract infections (ARTIs) in children that attend day-care centers.

Health Econ Rev 2019 May 7;9(1):12. Epub 2019 May 7.

Allergy & Immunology Service, Hospital Infantil de Mexico "Federico Gomez", Dr. Marquez 162, CP 06720, Mexico City, Mexico.

Background: Children that attend day-care centers frequently contract acute respiratory tract infections (ARTIs). ARTIs represent a burden for both children and parents. Systematic reviews on the use of immunostimulants for the prevention of juvenile recurrent ARTIs have provided moderate evidence of efficacy and safety. The aim of the study was to establish whether the immunostimulant, OM-85, was cost-effective in preventing ARTIs in children 2-6 years old that attended day-care centers or preschools in Mexico. We performed a systematic review to evaluate the efficacy of OM-85. For costs, we assumed an institutional perspective, which included the costs of care and supplies over a study period of six months, during the autumn-winter seasons. We created decision trees and constructed a model to identify pharmacoeconomic parameters. We generated 1000 estimations with the bootstrap method to calculate descriptive statistics of pharmacoeconomic parameters. We evaluated cost-effectiveness compared to treatment without immunostimulants.

Results: The mean (SD) incidences of ARTIs were 5.59 ± 0.29 without immunostimulants and 2.97 ± 0.32 with OM-85, during the study period. The mean (25th, 75th percentile) direct costs of ARTIs were 57.04 (37.11, 76.39) US$ (US dollars) without immunostimulants and 48.53 (37.35, 58.93) US$ with OM-85, with a mean increment of - 8.51(- 17.08, 0.75) US$, and a mean cost-effectiveness of - 17.94 (- 36.48, 1.66) US$. The direct costs plus the cost of one parent missing work to care for the child with ARTI were 125.76 (102.83, 150.16) US$, without immunostimulant and 85.21 (72.15, 98.81) US$, with OM-85. The increment was - 40.55 (- 68.29, - 13.95) US$, and the cost-effectiveness was - 86.89 (- 142.37, - 29.34) US$.Part of the cost reduction was ascribed to the reduced use of medications, particularly antibiotics.

Conclusions: Our results were consistent with previous clinical studies conducted in closed institutions in Mexico. OM-85 reduced the number of ARTIs and the frequency of antibiotics use. We concluded that OM-85 was cost-effective for preventing ARTIs in children that attended day-care centers, particularly when parental absenteeism was covered by the institutions.
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http://dx.doi.org/10.1186/s13561-019-0230-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734393PMC
May 2019

Effect of omega-3 fatty acids supplementation combined with lifestyle intervention on adipokines and biomarkers of endothelial dysfunction in obese adolescents with hypertriglyceridemia.

J Nutr Biochem 2019 02 7;64:162-169. Epub 2018 Nov 7.

Department of Pharmacobiology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.

Obesity in adolescents is considered a major public health problem; combined interventional approaches such as omega-3 supplementation with lifestyle intervention (LI) might exert synergistic effects and exceed the impact of each individual strategy. The purpose of the present study was to evaluate if the supplementation of omega-3 with LI could improve metabolic and endothelial abnormality in obese adolescents with hypertriglyceridemia. The study involved sixty-nine adolescents with normal weight and seventy obese adolescents with hypertriglyceridemia. All obese adolescents were applied to LI and randomly assigned to omega-3 supplementation or placebo group for 12 weeks. The obese adolescents with hypertriglyceridemia presented increased levels of leptin, retinol binding protein 4 (RBP4), selectin E (sE) and asymmetric dimethylarginine (ADMA) and decreased levels of adiponectin compared with control subjects. After 12-week intervention, omega-3 supplementation with LI decreased significantly in triglycerides, HOMA, leptin, RBP4, ADMA and sE. Moreover, omega-3 with LI displayed a significant reduction in triglycerides, ADMA and sE in comparison with LI alone. In subjects with omega-3 combined with LI assessed by multivariate regression model, the reduction in triglycerides was the only independent determinant of the decrease in ADMA. The reductions in triglycerides and HOMA were significantly contributed to the changes in sE. Our data indicated that omega-3 combined with LI in short duration significantly improved dyslipidemia, insulin resistance, abnormality of adipokines, endothelial dysfunction in comparison of LI alone, indicating the combined approach is an effective clinical and applicable strategy to control metabolic abnormality and decrease the risks of cardiovascular diseases in obese adolescents.
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http://dx.doi.org/10.1016/j.jnutbio.2018.10.012DOI Listing
February 2019

An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos.

J Allergy Clin Immunol 2019 03 7;143(3):957-969. Epub 2018 Sep 7.

Veterans Caribbean Health Care System, San Juan, Puerto Rico.

Background: Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.

Objective: We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.

Methods: We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.

Results: We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10, combined P = 2.6 × 10). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P < .001). In addition, lower expression of SMAD2 was associated with more frequent exacerbations among Puerto Ricans with asthma.

Conclusion: Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations.
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http://dx.doi.org/10.1016/j.jaci.2016.08.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927816PMC
March 2019

Pediatric asthma treatment: What to do when international guideline recommendations do not agree.

Ann Allergy Asthma Immunol 2018 07 15;121(1):7-13.e4. Epub 2018 Mar 15.

Allergy Department, Hospital Regional Lic. Adolfo López Mateos, ISSSTE, Mexico City, Mexico.

Background: There was a need for a solid asthma guideline in Mexico to update and unify asthma management. Because high-quality asthma guidelines exist worldwide, in which the latest evidence on asthma management is summarized, the ADAPTE approach allows for the development of a national asthma guideline based on evidence from already existing guidelines, adapted to national needs.

Objective: To fuse evidence from the best asthma guidelines and adapt it to local needs with the ADAPTE approach.

Methods: The Appraisal of Guidelines for Research and Evaluation (AGREE) II asthma guidelines were evaluated by a core group to select 3 primary guidelines. For each step of asthma management, clinical questions were formulated and replied according to (1) evidence in the primary guidelines, (2) safety, (3) Cost, and (4) patient preference. The Guidelines Development Group, composed of a broad range of experts from medical specialties, primary care physicians, and methodologists, adjusted the draft questions and replies in several rounds of a Delphi process and 3 face-to-face meetings, taking into account the reality of the situation in Mexico. We present the results of the pediatric asthma treatment part.

Results: Selected primary guidelines are from the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN), Global Initiative for Asthma (GINA), and Spanish Guidelines on the Management of Asthma (GEMA) 2015, with 2016 updates. Recommendations or suggestions were made for asthma treatment in Mexico. In this article, the detailed analysis of the evidence present in the BTS/SIGN, GINA, and GEMA sections on the (non) pharmacologic treatment of pediatric asthma, education, and devices are presented for 2 age groups: children 5 years or younger and children 6 to 11 years old with asthma.

Conclusion: For the pediatric treatment and patient education sections, applying the AGREE II and Delphi methods is useful to develop a scientifically sustained document, adjusted to the Mexican situation, as is the Mexican Guideline on Asthma.
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http://dx.doi.org/10.1016/j.anai.2018.03.008DOI Listing
July 2018

[Mexican Asthma Guidelines: GUIMA 2017].

Rev Alerg Mex 2017;64 Suppl 1:s11-s128

Secretaría de Salud, Instituto Nacional de Enfermedades Respiratorias, Dirección General. Ciudad de México, México.

Background: The need for a national guideline, with a broad basis among specialists and primary care physicians was felt in Mexico, to try unifying asthma management. As several high-quality asthma guidelines exist worldwide, it was decided to select the best three for transculturation.

Methods: Following the internationally recommended methodology for guideline transculturation, ADAPTE, a literature search for asthma guidelines, published 1-1-2007 through 31-12-2015 was conducted. AGREE-II evaluations yielded 3/40 most suitable for transculturation. Their compound evidence was fused with local reality, patient preference, cost and safety considerations to draft the guideline document. Subsequently, this was adjusted by physicians from 12 national medical societies in several rounds of a Delphi process and 3 face-to-face meetings to reach the final version.

Results: Evidence was fused from British Thoracic Society Asthma Guideline 2014, Global Initiative on Asthma 2015, and Guía Española del Manejo del Asma 2015 (2016 updates included). After 3 Delphi-rounds we developed an evidence-based document taking into account patient characteristics, including age, treatment costs and safety and best locally available medication.

Conclusions: In cooperation pulmonologists, allergists, ENT physicians, paediatricians and GPs were able to develop an evidence-based document for the prevention, diagnosis and treatment of asthma and its exacerbations in Mexico.
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http://dx.doi.org/10.29262/ram.v64i0.272DOI Listing
July 2019

Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance.

Endocr Res 2017 Aug 20;42(3):252-259. Epub 2017 Mar 20.

j Laboratory of Pharmacology and Toxicology, HIMFG , Mexico City , Mexico.

Purpose: The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS).

Materials And Methods: Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods.

Results: The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R=0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R=0.372, P=0.008). BMI-SDS was mildly associated with leptin (R=0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R=0.136, P=0.007).

Conclusions: Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.
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http://dx.doi.org/10.1080/07435800.2017.1294601DOI Listing
August 2017

[Knowledge of asthma: educational intervention with the 2014 GINA guide in primary care physicians].

Rev Alerg Mex 2016 Oct-Dec;63(4):358-364

Secretaría de Salud, Hospital Infantil de México Federico Gómez, Departamento de Alergia e Inmunología Clínica Pediátrica. Ciudad de México, México.

Background: Asthma is a public health problem in the world, so updating the guidelines for the diagnosis and treatment of asthma is based primarily on the practice of primary care physicians. Educational interventions are useful for increasing knowledge.

Objective: To compare the level of knowledge of asthma before and after an educational intervention.

Methods: A quasi-experimental prospective study was conducted in general and family practitioners and pediatricians who attended a training workshop on general aspects of asthma and current guidelines for diagnosis and treatment (GINA 2014). A questionnaire consisting of 11 multiple choice questions relating to fundamental aspects of the disease and diagnosis, classification, treatment and management of attacks, was used in two assessments, baseline and post-intervention.

Results: A total of 178 patients participated in the study, with knowledge pre-intervention at 25.5 points and post-intervention at 97.5 points on a scale of 100, with p < 0.05.

Conclusion: Educational interventions are inexpensive and effective tools to increase the knowledge of health professionals, and they have an impact on improving patient care.
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http://dx.doi.org/10.29262/ram.v63i4.196DOI Listing
December 2018

Adipokines, asymmetrical dimethylarginine, and pulmonary function in adolescents with asthma and obesity.

J Asthma 2017 03 23;54(2):153-161. Epub 2016 Jun 23.

f Department of Pharmacobiology , Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional , Mexico City , Mexico.

Objective: This study was to investigate whether the metabolic abnormalities of adipokines and asymmetrical dimethylarginine (ADMA) associate with pulmonary function deficits in adolescents with obesity and asthma.

Methods: This study enrolled 28 obese adolescents with asthma, 46 obese adolescents without asthma, 58 normal-weight adolescents with asthma, and 63 healthy control subjects. Serum levels of leptin, high-molecule-weight (HMW) adiponectin, retinol binding protein 4 (RBP4), asymmetrical dimethylarginine (ADMA), and pulmonary function were qualified.

Results: The obese subjects had higher levels of leptin and ADMA but lower levels of HMW adiponectin than the normal-weight subjects with or without asthma. The subjects with asthma had higher levels of RBP4 than those without asthma. The obese adolescents with asthma had lowest forced expiratory lung volume in the first second (FEV)/forced vital capacity (FVC) ratio among the four study groups. In all the study subjects and in the subjects with asthma alone, the FEV/FVC ratio associated negatively with leptin, however, such association was rendered non-significant when adjusted for BMI. The pulmonary function deficits associated inversely with BMI percentile in the subjects with asthma. However, the decreased FEV/FVC ratio was not correlated with HMW adiponectin, RBP4 or ADMA.

Conclusions: Our present study confirmed obstructive pattern of pulmonary function characterized by the reduced FEV/FVC ratio in the obese adolescents with asthma. These pulmonary deficits were associated inversely with the increased BMI percentile.
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http://dx.doi.org/10.1080/02770903.2016.1200611DOI Listing
March 2017

[Radiographic changes in children with primary immunodeficiency].

Rev Alerg Mex 2015 Jul-Sep;62(3):211-8

Hospital Infantil de México Federico Gómez, Secretaría de Salud, Distrito Federal, México.

Background: Although we have epidemiological information on primary immunodeficiencies (PID), the available information is meager in Mexico.

Objective: To provide epidemiological information on the delay in the diagnosis of PID and its correlation to chronic lung damage.

Material And Method: A retrospective, analytical study was done in patients 0-18 year old age diagnosed with PID for 11 years at the HIMFG (Hospital Infantil de Mexico Federico Gomez). The variables studied were: age at symptom onset, age at diagnosis, time from onset of symptoms to diagnosis, number of previous pneumonias and studies with radiographic chronic lung damage data.

Results: 48 patients were obtained after meeting inclusion criteria; 33 showed lung damage at diagnosis, antibody deficiency being the most affected group. Relating age of onset of symptoms and the time difference of the onset of symptoms to diagnosis showed a strong correlation (p < 0.001, Rho > 0.80). A moderate correlation between the observed time difference vs number of pneumonias (p=0.005, Rho=0.495) and correlation between number of pneumonia and lung damage was highly significant (p <0.001, Rho=0.704).

Conclusion: A strong relationship between the elapsed time from onset of symptoms and the number of pneumonia with lung injury time was found. So, the recurrent pneumonia (> 2) must make suspect the diagnosis of PID, as recommended in the literature.
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August 2015

[Antihistamines for the treatment of urticaria in Mexico].

Rev Alerg Mex 2015 Jul-Sep;62(3):157-74

Clínica de Alergia, Asma y Pediatría del Sur, Hospital Médica Sur, Distrito Federal, México.

There are four types of histamine receptors. Allergic symptoms, especially those in rhinoconjunctivitis and urticaria, are mainly caused by activation of histamine receptor 1 (H1). Consequently, oral H1-antihistamines form and integral part of the treatment of these diseases. Antihistamines are inverse agonists that stabilize the non-active configuration of the histamine receptor. First generation H1-antihistamines cause a variety of adverse effects via several mechanisms: sedation (accumulation in the central nervous system), dry mouth, urinary retention, weight gain (low selectivity: stimulation of serotonin/muscarinic/alpha-adrenergic receptors) and drug interactions (substrate of CYP450-3A4). Generally second generation H1-antihistamines have a better safety profile. New guidelines on allergic rhinitis and urticaria recommend second generation H1-antihistamines as first line drugs, with -if necessary- four-times updosing to obtain control in urticaria. The enhanced efficacy of quadruple doses in urticaria, while maintaining a good safety profile, has been shown for bilastine, desloratadine and levocetirizine (rupatadine). For ebastine and fexofenadine only the safety of quadruple doses has been shown till now. Extreme precaution should be taken with astemizol and terfenadine that never should be up-dosed, as high serum concentrations can cause potentially fatal ventricular tachycardia. First generation antihistamines are not recommended as first line treatment and updosing is not safe.
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August 2015

[Nutritional implications of elimination diets].

Bol Med Hosp Infant Mex 2015 Mar - Apr;72(2):112-117. Epub 2015 Jun 6.

Servicio de Alergia e Inmunología Clínica Pediátrica, Hospital Infantil de México Federico Gómez, México D.F., México.

Background: The backbone of food allergy treatment is the restriction of causative foods. These interventions have shown that children who restrict the consumption of basic foods have a higher risk of malnutrition. The aim of the study was to identify the nutritional status of patients with elimination diet, characterizing their anthropometric indexes and identifying the percentage of patients in the group with true food allergies.

Methods: A cross-sectional study was carried out from January to October 2014 at the Hospital Infantil de Mexico Federico Gomez. Patients 1 to 11 years of age with a history of elimination of at least one of five foods (eggs, milk, wheat, corn, soybeans) for a minimum of 6 months were included. Full nutritional assessment was performed by comparing the anthropometric indexes to z score for age. Data analysis used descriptive statistics. Kruskal-Wallis and Spearman correlation were performed.

Results: The most frequent eliminated foods were milk, soy, eggs, corn, and wheat. Comparing the number of foods eliminated with different anthropometric indexes, with a greater amount of eliminated food, the z-score of weight/age (W/A), height/age (H/A) and weight/height (W/H) were lower and the most affected index was fat reserve. Only in 5% of children was food allergy confirmed.

Conclusions: The study confirms the need for nutrition counseling for patients who have elimination diets and overdiagnosis of food allergy.
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http://dx.doi.org/10.1016/j.bmhimx.2015.04.002DOI Listing
June 2015

[Food allergy diagnosis in patients with elimination diet history. Preliminary report].

Rev Alerg Mex 2014 Oct-Dec;61(4):298-304

Servicio de Alergia e Inmunología Clínica Pediátrica, Hospital Infantil de México Federico Gómez, México, DF.

Background: Food allergy diagnosis is performed by a double blind placebo controlled challenge; however, in a lot of patients, it is only based on clinical history, skin prick tests, or parents' perception. There is a high frequency of elimination diets without an adequate approach.

Objectives: To analyze the results of diagnostic tests in a group of children with elimination diet-based on suspected food allergy and verify such studies with double blind placebo-controlled test challenge.

Material And Method: An observational, analytical and prospective study was done in a group of patients with elimination diet for suspected food allergy. We performed prick test, Prick-to-Prick test and patch test and the positive ones were verified by double-blind placebo-controlled challenge.

Results: Fourty-three patients were included within a total of 1,935 tests. Both approach for immediate and late sensitivity had not statistically significant relationship between a positive test and the elimination of food. Until now, we had 4 (8%) positive challenges out of 50.

Conclusions: The frequency of allergy proved by double-blind placebo-controlled test in 50 challenges was of 8% (4/50), thus, in the preliminary report we found a high frequency of elimination diets without adequate support. It is very important that food allergy diagnosis is accurate and based on an appropriate approach; since the implementation of an elimination diet in pediatric population can have a negative influence on their growth and development.
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December 2014

[Frequency of allergy to cow's milk proteins and its association to other allergic diseases in patients of Hospital Infantil de Mexico Federico Gomez].

Rev Alerg Mex 2014 Oct-Dec;61(4):288-97

Hospital Infantil de México Federico Gómez, México, DF.

Background: The cow's milk protein allergy is the most common food allergy among children under two years and is associated with other atopic diseases.

Objectives: To evaluate cow's milk protein allergy frequency in patients sensitized to them, attended at the consultation of Immunology and Allergy in the Hospital Infantil de México Federico Gómez, and its association with other atopic diseases.

Material And Method: A cross-sectional, analytical and descriptive study that reviewed medical records of patients aged 0-19 years, attended at the consultation of Immunology and Allergy in the Hospital Infantil de México Federico Gómez, from January 2010 to January 2013, sensitized to the cow's milk protein by in vitro or in vivo studies, mediated or not by IgE, to determine its association with other atopic diseases during the course of their clinical evolution.

Results: We included 252 patients with symptoms suggestive of cow's milk protein allergy, which was diagnosed only in 15.1% by oral challenge. In relation to respiratory symptoms, about two-thirds of patients had rhinorrhea, nasal obstruction and nasal itching. Regarding gastrointestinal symptoms, about a third had abdominal pain, diarrhea and abdominal distension, being statistically significant. The most common dermatologic symptom, statistically significant, was xerosis. The most frequently associated atopic diseases were food allergy (76.3%), allergic rhinitis (65.8%), asthma (47.4%) and atopic dermatitis (23%).

Conclusions: The cow's milk protein allergy can be associated with other atopic diseases, such as allergy to other foods, allergic rhinitis, asthma and atopic dermatitis.
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December 2014

Effect of six-month lifestyle intervention on adiponectin, resistin and soluble tumor necrosis factor-α receptors in obese adolescents.

Endocr J 2014 17;61(9):921-31. Epub 2014 Jul 17.

Laboratory of Pharmacology and Toxicology, Hospital Infántil de México Federico Gómez (HIMFG), Mexico City 06720, Mexico.

The aim of this study was to evaluate the effect of a six-month lifestyle intervention on adiponectin, resistin, and two soluble forms of tumor necrosis factor-α receptor (sTNFR) in obese adolescents. A total of 54 obese adolescents aged 10 to 16 years completed the program. Twenty-four adolescents with normal weight at baseline were used as a control group. Our results demonstrated that obese adolescents had abnormal lipid profile, homeostasis model assessment (HOMA) index, adiponectin level (5.6 ± 2.7 vs. 7.6 ± 2.9 μg/mL, p = 0.005) as well as resistin level (31.0 ± 9.0 vs. 24.3 ± 8.5 ng/mL, p = 0.003), whereas levels of both sTNFRs were similar to those in normal weight subjects. After the six-month lifestyle intervention, obese adolescents had a slight but significant drop in standard deviation score-body mass index (SDS-BMI), a significant decrease in waist circumference, total cholesterol, triglycerides, HOMA index, as well as resistin, and a significant increase in adiponectin and high-density lipoprotein-cholesterol. In adolescents without decreased SDS-BMI, no change was observed in adipokines. Changes in adiponectin correlated negatively with changes in waist circumference (r = -0.275, p = 0.044). Changes in resistin correlated positively with changes in triglycerides (r = 0.302, p = 0.027). The study demonstrated the increase of resistin and the decrease of adiponectin in obese adolescents. Lifestyle intervention improved adipokine abnormalities in obese subjects.
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http://dx.doi.org/10.1507/endocrj.ej14-0157DOI Listing
January 2015

Lung function, airway inflammation, and polycyclic aromatic hydrocarbons exposure in mexican schoolchildren: a pilot study.

J Occup Environ Med 2014 Apr;56(4):415-9

From the National Institute of Public Health (Drs Barraza-Villarreal, Hernandez-Cadena, and Romieu and Ms Escamilla-Nuñez and Ms Schilmann), Cuernavaca, Morelos, Mexico; Centers for Disease Control & Prevention (Drs Li, Romanoff, and Sjödin); Atlanta, Ga; Hospital Infantil de Mexico Federico Gomez (Dr Del Río-Navarro), Mexico DF, Mexico; United States Environmental Protection Agency (Dr Díaz-Sanchez), Research Triangle Park, NC; Universidad Autónoma de San Luis Potosi (Dr Díaz-Barriga), San Luis Potosí, Mexico; Division of Clinical Sciences (Dr Sly), Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth; and International Agency for Research on Cancer (Dr Romieu), Lyon, France.

Objective: To determine the association of exposure to polycyclic aromatic hydrocarbons (PAHs) with lung function and pH of exhaled breath condensate (EBC) in Mexican schoolchildren.

Methods: A pilot study was performed in a subsample of 64 schoolchildren from Mexico City. Lung function and pH of EBC were measured and metabolites of PAHs in urine samples were determined. The association was analyzed using robust regression models.

Results: A 10% increase in the concentrations of 2-hydroxyfluorene was significantly negatively associated with forced expiratory volume in 1 second (-11.2 mL, 95% CI: -22.2 to -0.02), forced vital capacity (-11.6 mL, 95% CI: -22.9 to -0.2), and pH of EBC (-0.035, 95% CI: -0.066 to -0.005).

Conclusion: Biomarkers of PAHs exposure were inversely associated with lung function and decrease of ph of EBC as a marker of airway inflammation in Mexican schoolchildren.
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http://dx.doi.org/10.1097/JOM.0000000000000111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604599PMC
April 2014

CHRM2 but not CHRM1 or CHRM3 polymorphisms are associated with asthma susceptibility in Mexican patients.

Mol Biol Rep 2014 16;41(4):2109-17. Epub 2014 Jan 16.

Laboratory of Immunogenomics and Metabolic Diseases, Instituto Nacional de Medicina Genómica, SS, Periférico Sur 4809, Col. Arenal Tepepan, CP. 014610, Mexico City, Mexico.

Asthma is a complex disease for which genetic predisposition has been widely documented. Considerable evidence supports the hypothesis that polymorphisms in the muscarinic-cholinergic (CHRM) genes could be involved in asthma pathogenesis, bronchial hyperresponsiveness, and mucus secretion. To determine whether single nucleotide polymorphisms (SNPs) or haplotypes in CHRM1, CHRM2, or CHRM3 are associated with asthma in Mexican pediatric population. We performed a case-control study including 398 pediatric cases with asthma and 450 healthy controls. We analyzed 19 SNPs distributed among these three genes. Two of the seven SNPs located in CHRM2, the 3' untranslated region rs8191992 and rs6962027, differed significantly in allele frequencies between patients with asthma and healthy controls [odds ratio (OR) 1.42, 95 % confidence interval (95 % CI) 1.14-1.77, P = 0.001, and OR 1.50, 95 % CI 1.21-1.87, P = 0.0002, respectively]. Statistical significance remained after multiple comparison corrections (P = 0.003 and P = 0.005, respectively). The haplotypes AA and TT, containing both major and minor alleles from rs8191992 and rs6962027, also differed between cases and controls. The haplotype AA occurred at a lower frequency in cases (OR 0.67, 95 % CI 0.53-0.85, P = 0.001) whereas the haplotype TT was overrepresented in cases compared to controls (28 vs 21 %, respectively; OR 1.46, 95 % CI 1.15-1.85, P = 0.002). No association was observed between CHRM1 or CHRM3 SNPs or haplotypes and asthma. CHRM2 polymorphisms are implicated in the genetic etiology of asthma.
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http://dx.doi.org/10.1007/s11033-014-3060-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670879PMC
December 2014

Changes in ghrelin and asymmetrical dimethylarginine in obese Mexican adolescents after six-month lifestyle intervention.

Endocrine 2013 Jun 29;43(3):603-10. Epub 2012 Sep 29.

Department of Pharmacology and Toxicology, Hospital Infántil de México Federico Gómez (HIMFG), Mexico City, Mexico.

The aim of this study was to evaluate the effect of a six-month lifestyle intervention on ghrelin and asymmetrical dimethylarginine (ADMA) in obese Mexican adolescents. A total of 65 obese Mexican adolescents aged 10-16 years completed a six-month lifestyle intervention. Anthropometric and biochemical parameters were assessed at baseline and at six months. Twenty normal-weight adolescents were also evaluated at baseline. Insulin resistance (IR) was determined by the homeostasis model assessment of IR (HOMA-IR). Ghrelin and ADMA were determined by enzyme-linked immunosorbent assay. Obese adolescents presented significantly higher triglycerides, cholesterol, glucose, insulin, HOMA-IR, and ADMA levels, while ghrelin was significantly lower. The lifestyle intervention led to a significant improvement in HOMA-IR, ghrelin, and ADMA in the whole studied obese subjects. ADMA and ghrelin levels were associated with BMI and IR components. According to the value of HOMA-IR, the obese subjects were divided into subjects with or without IR, no difference in ghrelin and ADMA was observed in these two subgroups. After intervention, the obese with IR showed increased ghrelin and decreased ADMA, while the obese without IR only showed improvement in ghrelin. The multiple linear regression analysis revealed that the changes of systolic blood pressure were the only predictor for the changes of ghrelin in the obese with IR. Our study demonstrated the increase of ADMA and the decrease of ghrelin in obese adolescents. Lifestyle intervention improved insulin resistance, decreased ADMA, and increased ghrelin in obese subjects with IR although no significant weight loss was observed.
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http://dx.doi.org/10.1007/s12020-012-9808-7DOI Listing
June 2013

Plasminogen activator inhibitor-1, fibrinogen, and lung function in adolescents with asthma and obesity.

Endocr Res 2012 11;37(3):135-44. Epub 2012 May 11.

Department of Pharmacology and Toxicology, Hospital Infántil de México Federico Gómez (HIMFG), Mexico City, Mexico.

Background: Obesity promotes a low-grade systemic inflammatory state that may act on the lung to exacerbate asthma. There is little information on the relationship between systemic inflammation and lung function in children and adolescents.

Objectives: To explore the relationship among fibrinogen, plasminogen activator inhibitor-1 (PAI-1), lung function in adolescents with the presence of asthma, and/or obesity.

Methods: Totally 178 adolescents (boys and girls) were involved; four groups were divided according to their diagnosis: non-obese and non-asthmatic controls (n = 38), non-obese asthmatics (n = 31), obese non-asthmatics (n = 62), obese asthmatics (n = 47). The levels of PAI-1 and fibrinogen were determined in blood samples. The lung function was evaluated with spirometry by measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flows between 25 and75% (FEF(25-75%)).

Results: Compared to healthy controls, obese adolescents with or without asthma show higher levels of fibrinogen (289.2 ± 61.5, 328.4 ± 54.9, and 324.9 ± 68.9 mg/dL, respectively), PAI-1 (36.0 ± 17.3, 53.2 ± 22.3, and 52.6 ± 24.7 ng/mL, respectively), and the reduced FEV1/FVC ratio (87.7 ± 7.7, 81.6 ± 8.6, and 81.7 ± 6.9, respectively). In the whole studied subjects, FEV1/FVC ratio shows significant inverse correlation with PAI-1 (r = -0.185), fibrinogen (r = -0.157), body mass index (BMI; r = -0.303), insulin(r = -0.198), and HOMA (r = -0.173). In the 78 asthmatic subjects, FVC correlates positively with BMI.

Conclusion: Our data demonstrate that the degree of systemic inflammation and the degree of obesity in the whole studied adolescents groups correlate negatively with lung function, suggesting an obstructive pulmonary pattern. Further studies are needed to identify the pathophysiological mechanism for such association.
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http://dx.doi.org/10.3109/07435800.2012.654555DOI Listing
October 2012

[Disseminated Tuberculosis in an Infant with IFNg-IL-12/IL 23 Axis Defect].

Rev Alerg Mex 2012 Apr-Jun;59(2):86-92

Departamento de Alergia e InmunologÌa ClÌnica Pedi·trica, Hospital Infantil de MÈxico Federico GÛmez, MÈxico, D.F.

BCG vaccine contains low virulence Mycobacterium bovis bacillus. In Mexico it is given at birth with few reported adverse reactions in immunocompetent children; however, in immuno-compromised patients it can cause serious local or systemic adverse reactions. The most frequent related diseases include chronic granulomatous disease (CGD), human immunodeficiency virus infection (HIV), severe combined immunodeficiency (SCID) and mendelian susceptibility to mycobacterial disease (MSMD). At this time, the innate defect of the IFN-?/IL-12/IL-23 axis constitutes the main implied alteration in patients with MSMD. We present the case of an infant with disseminated mycobacterial infection and history of BCG given at birth and documentation of an altered functional study of the IFN-?/IL12/IL-23 axis, specifically at the IL-12 pathway, which is susceptible to improve with exogenous IFN-? administration. Treatment was started with antituberculous drugs plus subcutaneous IFN-?, with a marked clinical improvement. In children with disseminated infection by weakly virulent intracellular microorganisms, such as the species included in BCG vaccine, primary or secondary underlying immunodeficiency should be ruled out.
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April 2016

Carboplatin hypersensitivity and desensitization in an infant.

Ther Drug Monit 2010 Aug;32(4):525-8

Department of Allergy and Pediatric Immunology, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.

Although the reported incidence of carboplatin hypersensitivity is low, it is important to describe it because of its potentially fatal consequences. A 1-year-old Mexican girl weighing 10 kg who had optic nerve glioma was initially scheduled to receive 12 cycles of 600 mg/m2 carboplatin (CBP) as two 300-mg/m2 intravenous infusions administered over 1 hour on 2 different days and a 1-hour intravenous infusion of 1.5 mg/m2 vincristine every 4 weeks. The patient had no history of drug allergies or any type of adverse drug reaction, but she developed itchiness, maculopapular rash, sweating, respiratory distress, and anxiety during the seventh cycle of CBP. According to the algorithm developed by Naranjo et al, the adverse drug reaction was classified as definite secondary to CBP and confirmed by positive skin tests indicating hypersensitivity to the drug. After evaluating the clinical course of the adverse drug reaction and considering the need to continue cancer treatment, a decision was made to desensitize the patient to CBP. The desensitization procedure took 8 hours and was performed during each new chemotherapy cycle until the 12 cycles of chemotherapy were successfully completed. In summary, a case of CBP hypersensitivity in a 1-year-old girl who was successfully desensitized to CBP is reported.
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http://dx.doi.org/10.1097/FTD.0b013e3181dbdf8eDOI Listing
August 2010

Effect of losartan on vascular function in fructose-fed rats: the role of perivascular adipose tissue.

Clin Exp Hypertens 2010 Jan;32(2):98-104

Department of Pharmacology and Toxicology, Hospital Infantil de México Federico Gómez, México.

Recent studies have shown the effect of perivascular adipose tissue (PVAT) on the regulation of vascular function; however, its role in the model of metabolic syndrome remains unclear. The aim of this study was to examine the effect of losartan on PVAT-derived vascular dysfunction in fructose-induced hypertensive rats. Rats were fed with either water, 10% fructose, or 10% fructose with 10mg/kg losartan for 8 weeks. In the isolated aorta with PVAT and endothelium, contraction induced by norepinephrine (NE) was more potent in fructose-fed rats compared to control rats. Losartan normalized blood pressure, insulin resistance, and NE-induced vasoconstriction in fructose-fed rats. In the aortic rings with/without endothelium and with/without PVAT, losartan could not improve the acetylcholine-induced relaxation in fructose-fed rats. The observation suggested that losartan partly improved the PVAT-associated vascular regulation in fructose-induced hypertensive rats.
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http://dx.doi.org/10.3109/10641960902993129DOI Listing
January 2010

[Rhinitis, sinusitis and allergy].

Rev Alerg Mex 2009 Nov-Dec;56(6):204-16

Departamento de Alergia e Inmunología Clínica, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, colonia Doctores, CP 06720, México, DF.

The allergic and infectious diseases of the nasal mucous represent two of the most frequent and chronic upper airways diseases in children and young adults. They are a public health problem of great magnitude due to the high prevalence that causes a great welfare pressure in terms of ambulatory consultations, significant deterioration of the quality of life so much for the patient who suffers them, like for the relatives and affect the community for the high socioeconomic costs that these generate. It is indispensable to know the physiopathology to be able to realize in time a suitable diagnosis and with it to offer a treatment adapted to diminish it recurrence.
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February 2010

[Risk factors of food allergy].

Rev Alerg Mex 2009 Sep-Oct;56(5):158-64

Servicio de Alergia e Inmunología Clínica Pediátrica, México.

Food allergy or allergic food hypersensitivity is defined as an adverse immunologic reaction caused by immunologic mechanisms mediated or not by IgE. It is a complex disease influenced by polygenetic heritance and environmental factors. Many risk factors have been investigated, pre natal and post natal, and variable and controversial results have been obtained. The most important risk factors associated with food allergy are atopy, lack of breast feeding at least three to six months and early weaning (before four-six months).
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March 2010

Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans.

J Allergy Clin Immunol 2010 Feb 11;125(2):321-327.e13. Epub 2009 Nov 11.

Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.

Background: More than 200 asthma candidate genes have been examined in human association studies or identified with knockout mouse approaches. However, many have not been systematically replicated in human populations, especially those containing a large number of tagging single nucleotide polymorphisms (SNPs).

Objective: We comprehensively evaluated the association of previously implicated asthma candidate genes with childhood asthma in a Mexico City population.

Methods: From the literature, we identified candidate genes with at least 1 positive report of association with asthma phenotypes in human subjects or implicated in asthma pathogenesis using knockout mouse experiments. We performed a genome-wide association study in 492 asthmatic children aged 5 to 17 years and both parents using the Illumina HumanHap 550v3 BeadChip. Separate candidate gene analyses were performed for 2933 autosomal SNPs in the 237 selected genes by using the log-linear method with a log-additive risk model.

Results: Sixty-one of the 237 genes had at least 1 SNP with a P value of less than .05 for association with asthma. The 9 most significant results were observed for rs2241715 in the gene encoding TGF-beta1 (TGFB1; P = 3.3 x 10(-5)), rs13431828 and rs1041973 in the gene encoding IL-1 receptor-like 1 (IL1RL1; P = 2 x 10(-4) and 3.5 x 10(-4)), 5 SNPs in the gene encoding dipeptidyl-peptidase 10 (DPP10; P = 1.6 x 10(-4) to 4.5 x 10(-4)), and rs17599222 in the gene encoding cytoplasmic FMR1 interacting protein 2 (CYFIP2; P = 4.1 x 10(-4)). False discovery rates were less than 0.1 for all 9 SNPs. Multimarker analysis identified TGFB1, IL1RL1, the gene encoding IL-18 receptor 1 (IL18R1), and DPP10 as the genes most significantly associated with asthma.

Conclusions: This comprehensive analysis of literature-based candidate genes suggests that SNPs in several candidate genes, including TGFB1, IL1RL1, IL18R1, and DPP10, might contribute to childhood asthma susceptibility in a Mexican population.
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http://dx.doi.org/10.1016/j.jaci.2009.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823974PMC
February 2010

[Difficult-to-control asthma. A bibliographical review].

Rev Alerg Mex 2009 Jul-Aug;56(4):115-23

Servicio de Alergia e Inmunología Clínica, Hospital Infantil de México Federico Gómez.

Difficult-to-control asthma is a disease that causes serious exacerbations, near-fatal attacks, frequent hospitalizations, and needs chronic use of high doses of inhaled corticosteroids or daily oral corticosteroid therapy. On the basis of epidemiological studies, the risk factors for serious asthma are: female gender, high BMI, sensitivity to aspirin, gastro esophageal reflux, sinusitis, pneumonia history, and beginning of asthma symptoms in adult late age. It has been found that in severe asthma the inflammatory profile commonly changes with major participation of neutrophils, and evidence of destruction and remodelling. The first step in the care of these patients is an evaluation to determine that asthma is the right diagnosis. A systematic and rigorous evaluation helps to asses adequately the differential diagnoses, the comorbilities and the unusual triggers. The aim of the treatment is to achieve the best results with minimum adverse effects. New immunomodulatory therapies are needed for these patients management.
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October 2009

Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children.

PLoS Genet 2009 Aug 28;5(8):e1000623. Epub 2009 Aug 28.

Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.

Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.
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http://dx.doi.org/10.1371/journal.pgen.1000623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722731PMC
August 2009
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