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Association study of 15 novel single-nucleotide polymorphisms of the T-bet locus among Finnish asthma families.

https://arctichealth.org/en/permalink/ahliterature179237
Source
Clin Exp Allergy. 2004 Jul;34(7):1049-55
Publication Type
Article
Date
Jul-2004
Author
E. Ylikoski
R. Kinos
N. Sirkkanen
M. Pykäläinen
J. Savolainen
L A Laitinen
J. Kere
T. Laitinen
R. Lahesmaa
Author Affiliation
Centre for Biotechnology, University of Turku and Abo Akademi University, Finland. emmi.ylikoski@btk.utu.fi
Source
Clin Exp Allergy. 2004 Jul;34(7):1049-55
Date
Jul-2004
Language
English
Publication Type
Article
Keywords
Asthma - genetics - immunology
Chi-Square Distribution
Female
Finland
Humans
Immunoglobulin E - blood
Linkage Disequilibrium
Male
Polymorphism, Single Nucleotide
T-Box Domain Proteins
Transcription Factors - genetics - immunology
Abstract
T-box expressed in T cells (T-bet) is a transcription factor regulating the commitment of T helper (Th) cells by driving the cells into the Th1 direction. Abnormal Th1/Th2 balance may lead to complex disorders like asthma or autoimmune diseases. Recent studies have suggested that T-bet might be a candidate gene for asthma. This led us to screen 23 Finnish individuals for single-nucleotide polymorphisms (SNPs) in the T-bet locus and study the association between the SNPs and high serum IgE level and asthma.
We screened all six exons, adjacent intronic areas and 2 kb of the 5'-flanking region from 23 individuals utilizing WAVE trade mark technology. To explore whether T-bet is associated in serum IgE regulation or asthma we genotyped the SNPs in a Finnish asthmatic founder population. The association analyses were made using haplotype pattern mining.
Fifteen novel SNPs were found in the T-bet gene. Within the Finnish asthmatic founder population, there was no association between T-bet SNPs and high serum IgE level or asthma.
The genetic variability in the T-bet gene does not play a role in the pathogenesis of human asthma. Our results provide a novel panel of SNPs in T-bet and will help determine whether the SNPs have a functional role in other T cell-mediated diseases.
PubMed ID
15248849 View in PubMed
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Association study of the chromosomal region containing the FCER2 gene suggests it has a regulatory role in atopic disorders.

https://arctichealth.org/en/permalink/ahliterature199219
Source
Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):700-6
Publication Type
Article
Date
Mar-2000
Author
T. Laitinen
V. Ollikainen
C. Lázaro
P. Kauppi
R. de Cid
J M Antó
X. Estivill
H. Lokki
H. Mannila
L A Laitinen
J. Kere
Author Affiliation
Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland. tarja.laitinen@helsinki.fi
Source
Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):700-6
Date
Mar-2000
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alleles
Asthma - genetics - immunology
Chromosome Mapping
Chromosomes, Human, Pair 19
Cross-Cultural Comparison
Female
Finland
Genes, Regulator - genetics
Genetic Markers - genetics
Genetics, Population
Haplotypes
Humans
Male
Middle Aged
Phenotype
Polymerase Chain Reaction
Polymorphism, Genetic - genetics
Receptors, IgE - genetics
Respiratory Hypersensitivity - genetics - immunology
Spain
Abstract
On the basis of studies with animal models, the gene for the low-affinity receptor for immunoglobulin E (IgE) (FCER2, CD23) has been implicated as a candidate for IgE-mediated allergic diseases and bronchial hyperreactivity, or related traits. Given evidence for genetic complexity in atopic disorders, we sought to study two European subpopulations, Finnish and Catalonian. We studied three phenotypic markers: (1) total serum IgE level; (2) asthma; and (3) specific IgE level for a mixture of the most common aeroallergens in Finland. Altogether, eight polymorphic markers spanning a region of 10 cM around the FCER2 gene on chromosome 19p13 were analyzed in 124 families. The physical order of the markers and the location of the FCER2 gene were confirmed by using radiation hybrids. The allele and haplotype association study showed a suggestive haplotype association (significance of p
PubMed ID
10712310 View in PubMed
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Genetic control of serum IgE levels and asthma: linkage and linkage disequilibrium studies in an isolated population.

https://arctichealth.org/en/permalink/ahliterature207467
Source
Hum Mol Genet. 1997 Nov;6(12):2069-76
Publication Type
Article
Date
Nov-1997
Author
T. Laitinen
P. Kauppi
J. Ignatius
T. Ruotsalainen
M J Daly
H. Kääriäinen
L. Kruglyak
H. Laitinen
A. de la Chapelle
E S Lander
L A Laitinen
J. Kere
Author Affiliation
Department of Medical Genetics, Haartman Institute, Haartmaninkatu 3, 00014 University of Helsinki, Helsinki, Finland.
Source
Hum Mol Genet. 1997 Nov;6(12):2069-76
Date
Nov-1997
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Asthma - blood - genetics
Chromosome Mapping
Female
Finland
Genetic Linkage
Haplotypes
Humans
Immunoglobulin E - blood - genetics
Interleukin-9 - genetics
Linkage Disequilibrium
Male
Middle Aged
Pedigree
Selection Bias
Abstract
Immunoglobulin E (IgE) concentration in serum is elevated in atopic diseases such as asthma. A large genomic region on chromosome 5 has previously been implicated in the control of IgE levels and bronchial hyperreactivity and may, therefore, harbor genes predisposing to asthma. In an effort to confirm this linkage and to delimit the critical region, we took advantage of an isolated founder subpopulation in Finland to study genetic linkage and haplotype associations. Sixteen polymorphic markers, including the Interleukin-4 and -9 genes (IL4, IL9), were physically ordered and genotyped in 157 nuclear families. Genetic linkage studies involving sib- and cousin-pair analyses found no evidence of genetic linkage between markers in 5q and either serum IgE levels or asthma. Haplotype association studies were also performed. Although initial inspection suggested the possibility of linkage disequilibrium in the region of IL9, we developed a rigorous permutation test for assessing association and determined that the association was no greater than would be expected by chance. Sequence analysis of the IL9 gene in three patients sharing a possibly conserved haplotype revealed a T113M coding polymorphism, but this variant showed no association with either serum IgE levels or asthma. We conclude that allelic variation at chromosome 5q31 is not likely to contribute to inheritance of serum IgE levels or the development of asthma in this Finnish subpopulation.
PubMed ID
9328470 View in PubMed
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Phenotyping asthma patients for a gene mapping study in Finland.

https://arctichealth.org/en/permalink/ahliterature205284
Source
Clin Exp Allergy. 1998 Apr;28 Suppl 1:40-2; discussion 65-6
Publication Type
Article
Date
Apr-1998

A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population.

https://arctichealth.org/en/permalink/ahliterature194899
Source
Nat Genet. 2001 May;28(1):87-91
Publication Type
Article
Date
May-2001
Author
T. Laitinen
M J Daly
J D Rioux
P. Kauppi
C. Laprise
T. Petäys
T. Green
M. Cargill
T. Haahtela
E S Lander
L A Laitinen
T J Hudson
J. Kere
Author Affiliation
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland. tarja.laitinen@helsinki.fi
Source
Nat Genet. 2001 May;28(1):87-91
Date
May-2001
Language
English
Publication Type
Article
Keywords
Asthma - epidemiology - genetics
Chromosome Mapping
Chromosomes, Human, Pair 7 - genetics
Female
Finland - epidemiology
Founder Effect
Genetic Linkage
Genetic markers
Genetic Predisposition to Disease
Genome, Human
Humans
Hypersensitivity, Immediate - epidemiology - genetics
Immunoglobulin E
Male
Pedigree
Abstract
The genetics of asthma and atopy have been difficult to determine because these diseases are genetically heterogeneous and modified by environment. The pedigrees in our study (n=86) originate in eastern central Finland (Kainuu province). According to census records, this region had only 200 households (2,000 inhabitants) in the mid sixteenth to mid seventeenth centuries. The current population of 100,000 represents the expansion of these founders within the past 400 years. Because this population is relatively homogeneous, we hypothesized that the molecular genetic mechanisms underlying asthma might also have reduced heterogeneity and therefore be easier to dissect than in mixed populations. A recent twin family study supported a strong genetic component for asthma in Finland. We carried out a genome-wide scan for susceptibility loci in asthma in the Kainuu subpopulation. We identified two regions of suggestive linkage and studied them further with higher-density mapping. We obtained evidence for linkage in a 20-cM region of chromosome 7p14-p15 for three phenotypes: asthma, a high level of immunoglobulin E (IgE; atopy) and the combination of the phenotypes. The strongest linkage was seen for high serum IgE (non-parametric linkage (NPL) score 3.9, P=0.0001), exceeding the threshold for genome-wide significance based on simulations. We also observed linkage between this locus and asthma or atopy in two independent data sets.
PubMed ID
11326283 View in PubMed
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Two functional variants of the superoxide dismutase genes in Finnish families with asthma.

https://arctichealth.org/en/permalink/ahliterature15201
Source
Thorax. 2004 Feb;59(2):116-9
Publication Type
Article
Date
Feb-2004
Author
V L Kinnula
S. Lehtonen
P. Koistinen
S. Kakko
M. Savolainen
J. Kere
V. Ollikainen
T. Laitinen
Author Affiliation
Department of Internal Medicine, University of Oulu and Oulu University Hospital, Finland. vuokko.kinnula@helsinki.fi
Source
Thorax. 2004 Feb;59(2):116-9
Date
Feb-2004
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Asthma - enzymology - genetics
Child
Child, Preschool
Female
Finland
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Infant
Male
Middle Aged
Mutation, Missense - genetics
Pedigree
Polymorphism, Genetic - genetics
Research Support, Non-U.S. Gov't
Superoxide Dismutase - genetics
Abstract
BACKGROUND: Functional polymorphisms in the genes encoding superoxide dismutases (SOD)-that is, superoxide scavenging antioxidant enzymes-may play an important role in the development of inflammatory airway diseases such as asthma. METHODS: The allele frequencies of two missense polymorphisms of SOD genes (Ala16Val in MnSOD (SOD2) and Arg213Gly in ECSOD (SOD3)) were investigated in Finnish patients with asthma and compared with family based controls. Both variants have been shown to be functionally interesting in the lung. The polymorphism at the exon-intron 3 boundary of a third SOD, CuZnSOD (SOD1), was also included in the analysis. RESULTS: None of the SOD genetic variants studied appeared to be major genetic regulators in the development of asthma. We could exclude all models of inheritance that increased the risk of asthma more than 1.2 fold for MnSOD*Val (frequency of allele 0.74 in the population) and more than 6.6 fold for ECSOD*Gly213 (frequency of allele 0.03 in the population) compared with non-carriers. For the intronic polymorphism in CuZnSOD, a relative risk of more than 3.3 (frequency of allele 0.10 in the population) could be excluded. CONCLUSIONS: It is highly unlikely that the functionally important genetic variants Ala16Val and Arg213Gly of SODs play a major role in the genetic susceptibility of asthma.
PubMed ID
14760150 View in PubMed
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Verification of self-reported asthma and allergy in subjects and their family members volunteering for gene mapping studies.

https://arctichealth.org/en/permalink/ahliterature203276
Source
Respir Med. 1998 Nov;92(11):1281-8
Publication Type
Article
Date
Nov-1998
Author
P. Kauppi
L A Laitinen
H. Laitinen
J. Kere
T. Laitinen
Author Affiliation
Department of Medicine, Helsinki University Central Hospital, Finland.
Source
Respir Med. 1998 Nov;92(11):1281-8
Date
Nov-1998
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Chromosome Mapping
Finland
Humans
Hypersensitivity - diagnosis - genetics
Middle Aged
Patient Participation
Patient Selection
Reimbursement, Incentive
Respiratory Function Tests
Retrospective Studies
Rhinitis, Allergic, Seasonal - diagnosis
Sensitivity and specificity
State Medicine - economics
Abstract
Studies which aim at mapping genes contributing to the development of asthma and atopy demand that hundreds of patients and their family members be assessed. In Finland, the Social Insurance Institution (SII) grants substantial reimbursement for medication to all patients who meet diagnostic criteria of asthma, which include a history of asthmatic symptoms and a measured reversibility of bronchial obstruction. To recruit a large number of asthma patients efficiently in a short period of time, we took advantage of the national reimbursement procedure and retrospectively collective data on patients' medical history and lung function test results at the time of diagnosis. First, we wanted to investigate if the reimbursements could be regarded as objective verification for self-reported asthma. Altogether 335 adult self-reported asthma patients were evaluated, 87% of them were verified as having chronic asthma. Reimbursement for medication showed a sensitivity of 95% and a specificity of 76% for verified asthma. Second, we were interested to see if self-reported nasal allergic symptoms or self-reported physician diagnosed allergic rhinitis were sensitive and specific measures of allergy. The self-reported allergic nasal symptoms had a poor specificity (31% in the proband group and 59% in the family members group) when compared to the allergy screening test (Phadiatop). The best verification for self-reported asthma was achieved by combining the information on self-reported disease, granted reimbursement by the SII and the medical records. For allergies, the specificity of self-reporting was far too low to be used alone, and a positive allergy screening test together with relevant symptoms was chosen as a marker of allergy.
PubMed ID
9926141 View in PubMed
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7 records – page 1 of 1.