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Airway inflammation among compost workers exposed to actinomycetes spores.

https://arctichealth.org/en/permalink/ahliterature271518
Source
Ann Agric Environ Med. 2015;22(2):253-8
Publication Type
Article
Date
2015
Author
Kari Kulvik Heldal
Lene Madsø
Wijnand Eduard
Source
Ann Agric Environ Med. 2015;22(2):253-8
Date
2015
Language
English
Publication Type
Article
Keywords
Actinobacteria - chemistry
Adult
Aerosols - toxicity
Air Pollutants, Occupational - toxicity
Biomarkers - blood
Female
Humans
Male
Middle Aged
Norway - epidemiology
Occupational Exposure
Pulmonary Surfactant-Associated Protein A - blood
Pulmonary Surfactant-Associated Protein D - blood
Respiratory Hypersensitivity - epidemiology - microbiology
Sewage
Spores, Bacterial - chemistry
Uteroglobin - blood
Abstract
To study the associations between exposure to bioaerosols and work-related symptoms, lung function and biomarkers of airway inflammation in compost workers.
Personal full-shift exposure measurements were performed on 47 workers employed at five windrow plants (n=20) and five reactor plants (n=27). Samples were analyzed for endotoxins, bacteria, fungal and actinomycetes spores. Health examinations were performed on workers and 37 controls before and after work on the day exposure was measured. The examinations included symptoms recorded by questionnaire, lung function by spirometry and nasal dimensions by acoustic rhinometry (AR). The pneumoproteins CC16, SP-D and SP-A were measured in a blood sample drawn at the end of the day.
The levels of endotoxins (median 3 EU/m(3), range 0-730 EU/m(3)) and actinomycetes spores (median 0.2 ? 10(6) spores/m(3), range 0-590 ? 10(6) spores/m(3)) were significantly higher in reactor plants compared to windrow plants. However, windrow composting workers reported more symptoms than reactor composting workers, probably due to use of respiratory protection. Exposure-response relationships between actinomycetes spores exposure and respiratory effects, found as cough and nose irritation during a shift, was significantly increased (OR 4.3, 95% CI 1.1-16, OR 6.1, 95% CI 1.5-25, respectively, p
PubMed ID
26094519 View in PubMed
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Association between surfactant protein A gene locus and severe respiratory syncytial virus infection in infants.

https://arctichealth.org/en/permalink/ahliterature58561
Source
J Infect Dis. 2002 Feb 1;185(3):283-9
Publication Type
Article
Date
Feb-1-2002
Author
Johan Löfgren
Mika Rämet
Marjo Renko
Riitta Marttila
Mikko Hallman
Author Affiliation
Department of Pediatrics and Biocenter Oulu, University of Oulu, Oulu, FIN-90014 Finland. johann.lofgren@oulu.fi
Source
J Infect Dis. 2002 Feb 1;185(3):283-9
Date
Feb-1-2002
Language
English
Publication Type
Article
Keywords
Alleles
Chromosome Mapping
Female
Genotype
Haplotypes
Humans
Infant, Newborn
Male
Proteolipids - chemistry - genetics
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactants - chemistry - genetics
Research Support, Non-U.S. Gov't
Respiratory Syncytial Virus Infections - genetics
Abstract
Respiratory syncytial virus (RSV) causes seasonal epidemics of bronchiolitis among susceptible infants. Surfactant protein A (SP-A), a lung C-type lectin involved in innate host defense, opsonizes RSV and enhances phagocytosis. The candidate gene approach was used to investigate association of SP-A polymorphism with susceptibility to severe RSV infection. Genotype analysis was done for 86 infants with severe RSV infection and 95 matched control subjects. A significant difference in the frequency of SP-A2 was observed. The SP-A2 allele 1A(3) was overrepresented in RSV-infected infants, compared with control subjects (5% vs. 0.5%; P =.006), whereas allele 1A was underrepresented (1% vs. 6%; P =.011). The allele pool in which lysine was amino acid 223 was overrepresented in infants with severe RSV infection (28% vs. 18%; P =.023), whereas the allele pool in which proline was amino acid 99 was underrepresented (5% vs. 16%; P =.001). These results indicate that a genetic association exists between SP-A gene locus and severe RSV infection.
PubMed ID
11807709 View in PubMed
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Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population.

https://arctichealth.org/en/permalink/ahliterature58782
Source
Am J Hum Genet. 2000 May;66(5):1569-79
Publication Type
Article
Date
May-2000
Author
M. Rämet
R. Haataja
R. Marttila
J. Floros
M. Hallman
Author Affiliation
Department of Pediatrics and Biocenter Oulu, University of Oulu, FIN-90014, Oulu, Finland.
Source
Am J Hum Genet. 2000 May;66(5):1569-79
Date
May-2000
Language
English
Publication Type
Article
Keywords
Alleles
Birth weight
Female
Finland
Gene Frequency - genetics
Genetic Predisposition to Disease - genetics
Genotype
Gestational Age
Glucocorticoids - therapeutic use
Haplotypes - genetics
Humans
Infant, Newborn
Infant, Premature
Introns - genetics
Logistic Models
Male
Matched-Pair Analysis
Proteolipids - genetics - physiology
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactants - genetics - physiology
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Respiratory Distress Syndrome, Newborn - genetics
Risk factors
Sequence Deletion - genetics
Sex Characteristics
Abstract
Respiratory-distress syndrome (RDS) in the newborn is a major cause of neonatal mortality and morbidity. Although prematurity is the most-important risk factor for RDS, the syndrome does not develop in many premature infants. The main cause of RDS is a deficiency of pulmonary surfactant, which consists of phospholipids and specific proteins. The genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the surfactant protein A (SP-A) gene locus and RDS in the genetically homogeneous Finnish population. In the present study, 88 infants with RDS and 88 control infants that were matched for degree of prematurity, prenatal glucocorticoid therapy, and sex were analyzed for SP-A genotypes. We show that certain SP-A1 alleles (6A2 and 6A3) and an SP-A1/SP-A2 haplotype (6A2/1A0) were associated with RDS. The 6A2 allele was overrepresented and the 6A3 allele was underrepresented in infants with RDS. These associations were particularly strong among small premature infants born at gestational age
PubMed ID
10762543 View in PubMed
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[Association of polymorphism genes of surfactant proteins in patients with influenza].

https://arctichealth.org/en/permalink/ahliterature271090
Source
Zh Mikrobiol Epidemiol Immunobiol. 2015 Nov-Dec;(6):71-7
Publication Type
Article
Author
Dudina KR
Kutateladze MM
Bokova NO
Znoiko OO
Abramov DD
Kelly EI
Yuschuk ND
Source
Zh Mikrobiol Epidemiol Immunobiol. 2015 Nov-Dec;(6):71-7
Language
Russian
Publication Type
Article
Keywords
Adult
Cardiovascular Diseases - epidemiology - mortality
Case-Control Studies
Comorbidity
Endocrine System Diseases - epidemiology - mortality
Female
Gene Expression
Genetic Association Studies
Humans
Influenza A Virus, H1N1 Subtype - genetics - immunology - isolation & purification
Influenza A Virus, H3N2 Subtype - genetics - immunology - isolation & purification
Influenza, Human - epidemiology - mortality
Lung Diseases - epidemiology - mortality
Male
Polymorphism, Single Nucleotide
Pulmonary Surfactant-Associated Protein A - genetics
Pulmonary Surfactant-Associated Protein B - genetics
Russia - epidemiology
Abstract
Evaluate role of gene polymorphisms of surfactant proteins in susceptibility and severity of influenza infection course in representatives of Moscow population. MATERIALS AND METHODS; 320 influenza patients, infected with various influenza virus strains, and 115 healthy individuals (control group),, were included into the study. Human DNA samples genotyping for determination of SFTPA2 gene rs1965708 and rs1059046, SFTPB gene rs1130866 polymorphisms was carried out using a modified method of "adjacent samples".
Most of the individuals of the control group and influenza patients are carries of alleles and genotypes rs1965708 and rs1059046 of SFTPA2 gene, rs1130866 of SFTPB gene, that have, based on scientific literature data, shown association with severe course of influenza A(H1N1) pdm09 and other inflammatory diseases of the respiratory tract. Generally, significant differences in frequency of occurrence of unfavorable genotypes CC rs1965708, AA rs1059046 of SFTPA2 gene and CC rs1130866 of SFTPB gene in influenza patients in comparison with individuals of the control group were not detected, that gives evidence on a high (from 19 to 51%) prevalence of these genotypes in the studied population. Allele C and genotype CC rs1965708 of SFTPA2 gene, allele A and genotype AA rs1059046 of SFTPA2 gene, allele C and genotype CC rs1130866 of SFTPB gene did not shown an association with severe course of A(H1N1) pdm09 influenza. The following pathology registered in most (88%) of the patients with severe course of influenza A (H1N1)pdm09: diseases of cardiovascilar (44%), endocrine (36%) and respiratory (12%) systems.
Because in most of the deceased patients due to severe course of A (H1N1)pdm09 influenza, diseases of cardiovascular, respiratory and endocrine system were detected, and an association of unfavorable disease outcome with the studied genetic markers was not detected, dominating risk factor of development of severe course and lethal outcome for A(H1N1)pdm09 influenza in the studied cohort was comorbidity.
PubMed ID
26950992 View in PubMed
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Degree of lung maturity determines the direction of the interleukin-1- induced effect on the expression of surfactant proteins.

https://arctichealth.org/en/permalink/ahliterature63986
Source
Am J Respir Cell Mol Biol. 2000 Mar;22(3):280-8
Publication Type
Article
Date
Mar-2000
Author
V. Glumoff
O. Väyrynen
T. Kangas
M. Hallman
Author Affiliation
Department of Pediatrics and Biocenter Oulu, University of Oulu, Oulu, Finland.
Source
Am J Respir Cell Mol Biol. 2000 Mar;22(3):280-8
Date
Mar-2000
Language
English
Publication Type
Article
Keywords
Amniotic Fluid - chemistry
Animals
Blotting, Western
Cycloheximide - pharmacology
Dactinomycin - pharmacology
Female
Fetus - chemistry - physiology
Gene Expression Regulation, Developmental - drug effects - physiology
Interleukin-1 - pharmacology
Lung - chemistry - growth & development - physiology
Organ Culture Techniques
Pregnancy
Protein Synthesis Inhibitors - pharmacology
Proteolipids - analysis - genetics
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactants - analysis - genetics
RNA, Messenger - analysis - genetics
Rabbits
Research Support, Non-U.S. Gov't
Abstract
Intra-amniotic interleukin (IL)-1 increases surfactant components in immature fetal lung, whereas high IL-1 after birth is associated with surfactant dysfunction. Our aim was to investigate whether the fetal age influences the responsiveness of surfactant proteins (SPs) to IL-1. Rabbit lung explants from fetuses at 19, 22, 27, and 30 d of gestation and 1-d-old newborns were cultured in serum-free medium in the presence of recombinant human (rh) IL-1alpha or vehicle. The influence of IL-1alpha on SP-A, -B, and -C messenger RNA (mRNA) content was dependent on the conceptional age. In very immature lung on Day 19, rhIL-1alpha (570 ng/ml for 20 h) increased SP-A, -B, and -C mRNA by 860+/-15%, 314+/-108%, and 64+/-17%, respectively. The increase in SP-A mRNA was evident within 4 to 6 h. IL-1alpha increased the SP-A concentration in alveolar epithelial cells and in the culture medium within 20 h. In contrast, at 27 to 30 d of gestation and in newborns, IL-1alpha decreased SP-C, -B, and -A mRNA by means of 64 to 67%, 48 to 59%, and 12 to 15%, respectively. SP-B protein decreased by 45 to 60%. The decrease in mRNA became evident within 8 to 12 h and was dependent on IL-1 concentration. On Day 27, IL-1alpha accelerated the degradation of SP-B mRNA in the presence of actinomycin D. IL-1 did not increase the degradation rate of SP-A mRNA unless both actinomycin D and cycloheximide were added to the explants. The present findings may explain some of the contrasting associations between inflammatory cytokines and lung diseases during the perinatal period. The determinants of the direction of the IL-1 effect on the expression of SPs remain to be identified.
PubMed ID
10696064 View in PubMed
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Genetic influences and neonatal lung disease.

https://arctichealth.org/en/permalink/ahliterature58414
Source
Semin Neonatol. 2003 Feb;8(1):19-27
Publication Type
Article
Date
Feb-2003
Author
Mikko Hallman
Ritva Haataja
Author Affiliation
Department of Pediatrics, University of Oulu, Kajaanintie 52A PL 5000, 90014, Oulu, Finland. mikko.hallman@oulu.fi
Source
Semin Neonatol. 2003 Feb;8(1):19-27
Date
Feb-2003
Language
English
Publication Type
Article
Keywords
Genetic Predisposition to Disease
Humans
Infant, Newborn
Mutation
Polymorphism, Genetic
Pulmonary Surfactant-Associated Protein A - genetics
Pulmonary Surfactant-Associated Protein B - genetics
Pulmonary Surfactant-Associated Proteins - genetics
Respiratory Distress Syndrome, Newborn - genetics
Abstract
Neonatal lung diseases may have a genetic background. The available studies mainly concentrate on surfactant proteins (SP-A, SP-B) and respiratory distress syndrome. Specific alleles of the SP-A and SP-B genes associate interactively with susceptibility to respiratory distress syndrome. This genetic impact on the condition is influenced by environmental, acquired and inherited factors. Other alleles and genotypes of SP-A and SP-D associate with severe respiratory infections in early infancy. Rare mutations causing an absence of the SP-B protein result in progressive respiratory failure. Dominant mutations of SP-C associate with chronic lung disease, with variable manifestations. The first steps towards unraveling the genetic network influencing the susceptibility to neonatal lung diseases are now being taken. Genes encoding multifunctional proteins in the distal lung are prime candidates for causing susceptibility to neonatal lung disease, including bronchopulmonary dysplasia.
PubMed ID
12667827 View in PubMed
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Human surfactant protein--A gene locus for genetic studies in the Finnish population.

https://arctichealth.org/en/permalink/ahliterature58633
Source
Dis Markers. 2000;16(3-4):119-24
Publication Type
Article
Date
2000
Author
M. Rämet
R. Haataja
R. Marttila
A M Hämäläinen
M. Knip
M. Hallman
Author Affiliation
Biocenter Oulu, Oulu, Finland.
Source
Dis Markers. 2000;16(3-4):119-24
Date
2000
Language
English
Publication Type
Article
Keywords
Alleles
Chromosomes, Human, Pair 10 - genetics
Codon - genetics
Comparative Study
Finland - epidemiology
Gene Frequency
Genes
Genetic markers
Genotype
Haplotypes - genetics
Humans
Infant, Newborn
Lung Diseases - epidemiology - genetics
Polymorphism, Genetic
Protein Isoforms - genetics
Proteolipids - genetics
Pseudogenes
Pulmonary Surfactant-Associated Protein A
Pulmonary Surfactant-Associated Proteins
Pulmonary Surfactants - genetics
United States
Abstract
Lung surfactant lowers the surface tension but surfactant proteins also have other functions. Surfactant protein A (SP-A) has a well-defined role in innate immunity. The gene locus for human SP-A genes is in chromosome 10q21 through q24 and consists of two highly homologous functional SP-A genes (SP-A1 and SP-A2) and a pseudogene. Several alleles that differ by a single amino acid have been identified for both SP-A genes. The SP-A gene locus has been shown to be sufficiently polymorphic for genetic studies in the American population. In this study, we analysed the SP-A allele frequencies in a Finnish population (n = 790) and found them to differ from the frequencies observed in US. Furthermore, we describe several new alleles for both SP-A genes. The heterozygosity indices and polymorphism information content values ranged between 0.50--0.62 indicating that SP-A gene locus is polymorphic enough for studies associating the locus with pulmonary diseases.
PubMed ID
11381191 View in PubMed
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Inflammatory and anti-inflammatory responsiveness of surfactant proteins in fetal and neonatal rabbit lung.

https://arctichealth.org/en/permalink/ahliterature58347
Source
Pediatr Res. 2004 Jan;55(1):55-60
Publication Type
Article
Date
Jan-2004
Author
Outi Vayrynen
Virpi Glumoff
Mikko Hallman
Author Affiliation
Department of Pediatrics and Biocenter Oulu, University of Oulu, Kajaanintie 52, 90220 Oulu, Finland. mikko.hallman@oulu.fi
Source
Pediatr Res. 2004 Jan;55(1):55-60
Date
Jan-2004
Language
English
Publication Type
Article
Keywords
Adrenal Cortex Hormones - pharmacology
Animals
Animals, Newborn
Dexamethasone - pharmacology
Female
Gene Expression - drug effects
Humans
Infant, Newborn
Interleukin-1 - pharmacology
Lung - embryology - immunology
Organ Culture Techniques
Pneumonia - drug therapy - immunology
Pregnancy
Pulmonary Surfactant-Associated Protein A - genetics
Pulmonary Surfactant-Associated Protein B - genetics
Pulmonary Surfactant-Associated Protein C - genetics
RNA, Messenger - analysis
Rabbits
Research Support, Non-U.S. Gov't
Respiratory Distress Syndrome, Newborn - drug therapy - immunology
Abstract
Spontaneous preterm birth due to intrauterine infection is associated with increased concentrations of cytokines in amniotic fluid and in the airways at birth. Intra-amniotic IL-1 induces fetal lung maturity, consistent with the decrease in the incidence of respiratory distress syndrome (RDS) in intrauterine inflammation. On the other hand, antenatal corticosteroid decreases the incidence of RDS in infants born prematurely. The aim of the present study was to investigate the interaction between IL-1 and glucocorticoid in the expression of the surfactant proteins SP-A, -B, and -C. Lung explants from rabbit fetuses at 22 (immature), 27 (transitional), and 30 (mature) d of gestation (term, 30-31 d) and on d 1 after term birth were cultured with dexamethasone (Dx), IL-1alpha, or vehicle in the presence or absence of actinomycin D. According to the present results, IL-1alpha and Dx additively increased the expression of SP-A and SP-B on d 22. Later in gestation, SP-B and SP-C were suppressed by IL-1, whereas glucocorticoid tended to increase the expression of SP-B and SP-C and prevented the IL-1-induced suppression of SP. IL-1alpha and steroid interactively increased the stability of SP mRNA compared with the single agonist, possibly explaining the additive effects on the SP mRNA levels. The present results reveal beneficial additive effects of glucocorticoid and cytokine on lung surfactant. They may explain some of the acute beneficial effects of glucocorticoid therapy in chorioamnionitis before premature birth and in inflammatory lung disease after birth.
PubMed ID
14605255 View in PubMed
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Maternal endotoxin-induced preterm birth in mice: fetal responses in toll-like receptors, collectins, and cytokines.

https://arctichealth.org/en/permalink/ahliterature87345
Source
Pediatr Res. 2008 Mar;63(3):280-6
Publication Type
Article
Date
Mar-2008
Author
Salminen Annamari
Paananen Reija
Vuolteenaho Reetta
Metsola Juhani
Ojaniemi Marja
Autio-Harmainen Helena
Hallman Mikko
Author Affiliation
Department of Pediatrics, University of Oulu, Oulu, FIN-90014, Finland. annamari.salminen@oulu.fi
Source
Pediatr Res. 2008 Mar;63(3):280-6
Date
Mar-2008
Language
English
Publication Type
Article
Keywords
Amniotic Fluid - immunology
Animals
Chemokine CCL2 - metabolism
Collectins - blood - metabolism
Cytokines - blood - metabolism
Extraembryonic Membranes - immunology
Female
Fetal Blood - immunology
Fetal Death
Fetus - immunology
Gestational Age
Immunohistochemistry
Inflammation - chemically induced - immunology - physiopathology
Interleukin-10 - metabolism
Interleukin-6 - metabolism
Lipopolysaccharides
Lung - embryology - immunology
Maternal-Fetal Exchange
Mice
Mice, Inbred C57BL
Placenta - immunology
Pregnancy
Premature Birth - etiology - immunology - physiopathology
Pulmonary Surfactant-Associated Protein A - metabolism
Pulmonary Surfactant-Associated Protein D - metabolism
Time Factors
Toll-Like Receptor 2 - metabolism
Toll-Like Receptor 4 - metabolism
Toll-Like Receptors - blood - metabolism
Tumor Necrosis Factor-alpha - metabolism
Uterine Diseases - chemically induced - immunology - physiopathology
Uterus - immunology
Abstract
Major cause of prematurity is spontaneous preterm birth (PTB) associated with intrauterine inflammation. Our aim was to establish a model of endotoxin Lipopolysaccharide-induced PTB of live-born pups and to study early immune activation in fetal and maternal compartments. Expression of several proteins that bind microbes (Toll-like receptors TLR4, TLR2; surfactant proteins SP-A, SP-D) was analyzed. At 16 or 17 d of gestation, C57BL/6 dams received a single dose of intraperitoneal LPS, leading to PTB within 17 h. Cytokine levels increased in maternal serum, followed by a modest increase in fetal serum and in amniotic fluid. In uterus, placenta, and fetal membranes, LPS mostly increased the expressions of TLR, SPs, and cytokines. The number of TLR2-positive macrophages increased in labyrinthine placenta. In fetal lung, intestine, liver, and brain there were modest changes in cytokine expressions. In fetal lung, SP and TLR mRNAs decreased and TLR2-positive macrophages redistributed around vessels. LPS-induced fetal deaths associated with early age (16 d gestation) rather than with proinflammatory activation. Here we propose that maternal LPS response leads to PTB and acute decrease of immune proteins in epithelial lining of fetal lung. Instead, acceleration of lung maturity has been previously observed in intraamniotic inflammation.
PubMed ID
18287966 View in PubMed
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A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis patients: clinical and genetic features.

https://arctichealth.org/en/permalink/ahliterature122050
Source
Respir Res. 2012;13:64
Publication Type
Article
Date
2012
Author
Bridget A Fernandez
George Fox
Rick Bhatia
Eric Sala
Barbara Noble
Nash Denic
Dzintra Fernandez
Nigel Duguid
Amanda Dohey
Fady Kamel
Laura Edwards
Krista Mahoney
Susan Stuckless
Patrick S Parfrey
Michael O Woods
Author Affiliation
Discipline of Genetics, Memorial University of Newfoundland, St John's, NL, Canada.
Source
Respir Res. 2012;13:64
Date
2012
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Aged
Aged, 80 and over
Bone Marrow Diseases - genetics
Cohort Studies
Female
Founder Effect
Genetic Association Studies
Humans
Idiopathic Pulmonary Fibrosis - diagnosis - epidemiology - genetics
Male
Middle Aged
Mutation
Newfoundland and Labrador - epidemiology
Pulmonary Surfactant-Associated Protein A - genetics
Pulmonary Surfactant-Associated Protein C - genetics
Telomerase - genetics
Young Adult
Abstract
Idiopathic pulmonary fibrosis (IPF) is an adult-onset Idiopathic Interstitial Pneumonia (IIP) usually diagnosed between age 50 to 70?years. Individuals with Familial Pulmonary Fibrosis (FPF) have at least one affected first or second-degree relative and account for 0.5-20% of cases.
We ascertained and collected DNA samples from a large population-based cohort of IPF patients from Newfoundland, Canada. For each proband, a family history was documented and medical records were reviewed. Each proband was classified as familial (28 patients) or sporadic (50 patients) and all 78 probands were screened for variants in four highly penetrant, adult-onset PF genes (SFTPC, SFTPA2, TERT,TERC).
Seventy-eight IPF probands were enrolled of whom 28 (35.9%) had a positive family history. These 28 familial patients led to the recruitment of an additional 49 affected relatives (total of 77 FPF patients). By age 60?years, 42% of the familial cohort had been diagnosed with PF compared with only 16% of the sporadic patient collection (?2?=?8.77, p?=?0.003). Mean age of diagnosis in the familial group was significantly younger than the sporadic group (61.4?years vs. 66.6?yrs, p?=?0.012) with a wider age range of diagnosis (19-92?years compared with 47-82?years). Thirty-three of 77 (42.8%) FPF patients had a tissue diagnosis and all but five had usual interstitial pneumonia histology. Compared with other published case series, the familial IIP histologies were more homogeneous. Three of 28 familial probands (10.7%) and none of the 50 sporadic probands had pathogenic variants in the four genes tested. All three familial probands had mutations in TERT. Other phenotypes associated with telomerase deficiency were present in these families including cirrhosis, bone marrow hypoplasia and premature graying. Telomere length assays were performed on mutation carriers from two families and confirmed telomere-related deficiency.
The proportion of familial cases in our cohort is higher than any previously reported estimate and we suggest that this is due to the fact that Newfoundland cohort is ethnically homogeneous and drawn from a founder population. In our patient collection, diagnosis with IPF prior to age 45?years predicted familial disease. In two of the three TERT mutation families, the pedigree appearance is consistent with genetic anticipation. In the other 25 FPF families negative for mutations in known PF genes, we did not identify other telomerase associated medical problems (bone marrow dysfunction, cirrhosis) and we hypothesize that there are novel PF genes segregating in our population.
Notes
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PubMed ID
22853774 View in PubMed
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19 records – page 1 of 2.