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Analysis of MHC region genetics in Finnish patients with juvenile idiopathic arthritis: evidence for different locus-specific effects in polyarticular vs pauciarticular subsets and a shared DRB1 epitope.

https://arctichealth.org/en/permalink/ahliterature184602
Source
Genes Immun. 2003 Jul;4(5):326-35
Publication Type
Article
Date
Jul-2003
Author
J A Runstadler
H. Säilä
A. Savolainen
M. Leirisalo-Repo
K. Aho
E. Tuomilehto-Wolf
J. Tuomilehto
M F Seldin
Author Affiliation
Rowe Program in Human Genetics and Molecular Medicine, Department of Biological Chemistry, University of California, Davis, USA. jarunstadler@ucdavis.edu
Source
Genes Immun. 2003 Jul;4(5):326-35
Date
Jul-2003
Language
English
Publication Type
Article
Keywords
Age of Onset
Arthritis, Juvenile - genetics
Case-Control Studies
Chromosomes, Human, Pair 6 - genetics
Finland
Gene Frequency
Genetic Predisposition to Disease
HLA-DR Antigens
HLA-DRB1 Chains
Humans
Linkage Disequilibrium - genetics
Major Histocompatibility Complex - genetics
Microsatellite Repeats - genetics
Sequence Analysis, DNA
Abstract
This study used Finnish juvenile idiopathic arthritis (JIA) probands with pauciarticular and rheumatoid factor (RF) negative polyarticular subtypes of JIA to further define the genetic susceptibility to JIA. We examined 16 markers spanning an 18 cM region of chromosome 6 encompassing the MHC and surrounding genomic region in a set of 235 Finnish JIA nuclear families and 639 Finnish control individuals. Analysis by case/control association and transmission disequilibrium test (TDT) methods each demonstrated strong evidence for a susceptibility locus near the D6S2447 microsatellite (P
PubMed ID
12847547 View in PubMed
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Chromosome 4q locus associated with insulin resistance in Pima Indians. Studies in three European NIDDM populations.

https://arctichealth.org/en/permalink/ahliterature218033
Source
Diabetes. 1994 Jun;43(6):800-4
Publication Type
Article
Date
Jun-1994
Author
P. Humphreys
M. McCarthy
J. Tuomilehto
E. Tuomilehto-Wolf
I. Stratton
R. Morgan
A. Rees
D. Owens
J. Stengård
A. Nissinen
Author Affiliation
Department of Medicine, Addenbrooke's Hospital, University of Cambridge, U.K.
Source
Diabetes. 1994 Jun;43(6):800-4
Date
Jun-1994
Language
English
Publication Type
Article
Keywords
Aged
Alleles
Base Sequence
Blood Glucose - metabolism
Carrier Proteins - genetics
Chromosome Mapping
Chromosomes, Human, Pair 4
DNA Primers
Diabetes Mellitus, Type 2 - blood - genetics
European Continental Ancestry Group - genetics
Fatty Acid-Binding Proteins
Fatty Acids - metabolism
Finland
Genetic Predisposition to Disease
Glucose Intolerance - genetics
Great Britain
Humans
Indians, North American - genetics
Insulin Resistance - genetics
Male
Molecular Sequence Data
Neoplasm Proteins
Polymorphism, Genetic
Reference Values
Tumor Suppressor Proteins
Wales
Abstract
Markers on chromosome 4q have recently been shown to be associated with insulin resistance in Pima Indians, a population in which insulin resistance precedes and predicts the development of non-insulin-dependent diabetes mellitus (NIDDM). To examine whether genes in this region could play a major role in susceptibility to NIDDM in other populations, we have examined the allele frequencies of a trinucleotide repeat near the fatty acid-binding protein 2 (FABP2) gene on 4q28-31 in three European populations: Finnish, U.K. Caucasian, and Welsh. The U.K. NIDDM population was selected for insulin resistance by studying patients whose obesity-corrected fasting plasma insulin before treatment was above the 98th percentile. Seven alleles were detected. On cross-tabulation analysis, there were no significant associations between allele frequencies and glucose intolerance in any of the populations. Log-linear analysis of the results from all three populations suggested a moderately significant interaction of glucose tolerance status (normal versus diabetic) and the FABP2 allele (partial chi 2 = 24, df 6, P = 0.027). The parameter describing the interaction of allele A3 and glucose tolerance status was the only such parameter differing significantly from zero (z-score +2.003, P = 0.046). In both the Finnish and U.K. population, the A3 allele was found approximately twice as frequently in NIDDM than in control subjects (Finnish control subjects, impaired glucose tolerance, and NIDDM: 12.2, 22.4, and 26.6%, respectively; U.K. control subjects and NIDDM: 7.8 and 14.6%, respectively). In the Finnish populations, no associations were found between FABP2 alleles and plasma insulin levels or with homeostatic model assessment (HOMA) estimates of beta-cell function and insulin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
PubMed ID
8194666 View in PubMed
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Coffee consumption as trigger for insulin dependent diabetes mellitus in childhood.

https://arctichealth.org/en/permalink/ahliterature229454
Source
BMJ. 1990 Mar 10;300(6725):642-3
Publication Type
Article
Date
Mar-10-1990
Author
J. Tuomilehto
E. Tuomilehto-Wolf
E. Virtala
R. LaPorte
Author Affiliation
Department of Epidemiology, National Public Health Institute, Helsinki, Finland.
Source
BMJ. 1990 Mar 10;300(6725):642-3
Date
Mar-10-1990
Language
English
Publication Type
Article
Keywords
Caffeine - adverse effects - metabolism
Coffee - adverse effects
Diabetes Mellitus, Type 1 - epidemiology - etiology - metabolism
Female
Finland - epidemiology
Humans
Maternal-Fetal Exchange
Pregnancy
Risk factors
Notes
Cites: J Pediatr. 1977 Jun;90(6):1022-3859052
Cites: Postgrad Med. 1977 Sep;62(3):64-9896615
Cites: Clin Pharmacol Ther. 1983 May;33(5):591-6026687705
Cites: Diabetes Care. 1987 Mar-Apr;10(2):238-483556107
Cites: World Health Stat Q. 1988;41(3-4):179-892466379
Comment In: BMJ. 1990 Apr 14;300(6730):10122344489
PubMed ID
2322701 View in PubMed
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Comparison of incidence of IDDM in childhood between Estonia and Finland, 1980-1988.

https://arctichealth.org/en/permalink/ahliterature225443
Source
Diabetes Care. 1991 Nov;14(11):982-8
Publication Type
Article
Date
Nov-1991
Author
J. Tuomilehto
T. Podar
A. Reunanen
I. Kalits
R. Lounamaa
E. Tuomilehto-Wolf
B. Adojaan
B. Neff
R E LaPorte
Author Affiliation
Department of Epidemiology, National Public Health Institute, Helsinki, Finland.
Source
Diabetes Care. 1991 Nov;14(11):982-8
Date
Nov-1991
Language
English
Publication Type
Article
Keywords
Adolescent
Age Factors
Child
Child, Preschool
Diabetes Mellitus, Type 1 - epidemiology
Estonia - epidemiology
Female
Finland - epidemiology
Humans
Incidence
Infant
Male
Regression Analysis
Sex Characteristics
Abstract
To compare nationwide incidence of childhood insulin-dependent diabetes mellitus (IDDM) in children aged 0-14 yr between Estonia and Finland during 1980-1988. For Estonia, which has a population genetically and linguistically related to Finland, only limited information was available. Finland has the highest incidence of IDDM in the world.
The registration of all new cases of IDDM in Estonia was conducted by the local district pediatricians who reported every newly diagnosed diabetic patient to the Republic Endocrinology Centre. Registration of all new cases of IDDM in Finland was based on the statistics of the Social Insurance Institution, which approves free-of-charge insulin treatment for diabetes. These data were validated with one or more additional data sources. The case ascertainment rate approached 100% in both countries.
The average yearly incidence of IDDM standardized for age for the years 1980-1988 in Estonia was approximately 33% of that in Finland. Among males it was 11.3 (95% confidence interval [CI] 10.3-12.3) per 100,000 in Estonia and 35.1 (95% CI 33.4-36.9) per 100,000 in Finland, and among females 10.1 (95% CI 9.2-11.1) per 100,000 in Estonia and 30.4 (95% CI 28.8-32.1) per 100,000 in Finland. When the two periods 1980-1982 and 1986-1988 were compared, the age-standardized incidence in Estonia remained unchanged, whereas in Finland it increased approximately 20%.
The data between two populations who are ethnically and linguistically similar and live geographically close but in a different environment, provides further evidence that both genetic and environmental factors are contributing to the risk of IDDM.
PubMed ID
1797512 View in PubMed
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DQA1 and DQB1 heterodimers in insulin-dependent diabetes mellitus: a genetic-epidemiological study in Finland. DiMe Study Group.

https://arctichealth.org/en/permalink/ahliterature222619
Source
Ann Med. 1992 Dec;24(6):533-8
Publication Type
Article
Date
Dec-1992
Author
E. Tuomilehto-Wolf
J. Tuomilehto
G A Hitman
Author Affiliation
Department of Epidemiology, National Public Health Institute, Helsinki, Finland.
Source
Ann Med. 1992 Dec;24(6):533-8
Date
Dec-1992
Language
English
Publication Type
Article
Keywords
Adolescent
Alleles
Child
Diabetes Mellitus, Type 1 - epidemiology - genetics
Disease Susceptibility
Female
Finland - epidemiology
HLA-DQ Antigens - genetics
HLA-DQ alpha-Chains
HLA-DQ beta-Chains
Humans
Macromolecular Substances
Male
Abstract
Susceptibility to insulin-dependent diabetes mellitus (IDDM) correlates with the absence of aspartic acid in position 57 of the DQB1 and/or the presence of arginine in position 52 of the DQA1. It has been postulated that transcomplementation between the DQ alpha and beta chains of the two haplotypes could create new molecules conferring susceptibility to IDDM. Finland has the highest incidence of IDDM in the world (35/100,000). In a nationwide study of IDDM in childhood (DiMe study) HLA genotyping using conventional serology was carried out according to genetic-epidemiological principles. We simulated DQA1 and DQB1 alleles in 707 consecutively diagnosed IDDM probands and 98 non-diabetic children based on serology, restriction fragment length polymorphism results and sequence data assuming no recombination between DQ and DR. In 34% of Finnish children with IDDM all four combinations (two in cis and two in trans) could lead to SS heterodimers. Two-thirds of these combinations were explained by DR3,DR4 heterozygotes. In 50% of IDDM children half and in 11% a quarter of the combinations could lead to heterodimers. In 38 IDDM patients (5%) the formation of hybrid molecules was not possible. In 59% of the controls SS heterodimers were possible and should therefore have an underlying genetic susceptible for IDDM assuming the theory of transcomplementation is correct. These findings, together with the fact that the lowest frequency of DR3,DR4 heterozygosity (21%) was seen in Finland, show that heterozygosity for DQ and DR cannot explain the differences seen in IDDM incidence.
PubMed ID
1485950 View in PubMed
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Epidemiology of childhood diabetes mellitus in Finland--background of a nationwide study of type 1 (insulin-dependent) diabetes mellitus. The Childhood Diabetes in Finland (DiMe) Study Group.

https://arctichealth.org/en/permalink/ahliterature224723
Source
Diabetologia. 1992 Jan;35(1):70-6
Publication Type
Article
Date
Jan-1992
Author
J. Tuomilehto
R. Lounamaa
E. Tuomilehto-Wolf
A. Reunanen
E. Virtala
E A Kaprio
H K Akerblom
Author Affiliation
Department of Epidemiology, University of Helsinki, Finland.
Source
Diabetologia. 1992 Jan;35(1):70-6
Date
Jan-1992
Language
English
Publication Type
Article
Keywords
Adolescent
Child
Child, Preschool
Demography
Diabetes Mellitus, Type 1 - epidemiology - genetics
Female
Finland - epidemiology
Humans
Incidence
Infant
Male
Prevalence
Prospective Studies
Registries
Sex Characteristics
Abstract
A nationwide study of childhood Type 1 (insulin-dependent) diabetes mellitus was established in 1986 in Finland, the country with the highest incidence of this disease worldwide. The aim of the project called "Childhood Diabetes in Finland" is to evaluate the role of genetic, environmental and immunological factors and particularly the interaction between genetic and environmental factors in the development of Type 1 diabetes. From September 1986 to April 1989, 801 families with a newly-diagnosed child aged 14 years or younger at the time of diagnosis were invited to participate in this study. The vast majority of the families agreed to participate in the comprehensive investigations of the study. HLA genotypes and haplotypes were determined in 757 families (95%). Our study also incorporates a prospective family study among non-diabetic siblings aged 3-19 years, and two case-control studies among the young-onset cases of Type 1 diabetes. During 1987-1989, the overall incidence of Type 1 diabetes was about 35.2 per 100,000 per year. It was higher in boys (38.4) than in girls (32.2). There was no clear geographic variation in incidence among the 12 provinces of Finland. Of the 1,014 cases during these 3 years only six cases were diagnosed before their first birthday. The incidence was high already in the age group 1-4-years old: 33.2 in boys and 29.5 in girls. Of the 801 families 90 (11.2%) were multiple case families, of which 66 had a parent with Type 1 diabetes at the time of diagnosis of the proband.(ABSTRACT TRUNCATED AT 250 WORDS)
PubMed ID
1541383 View in PubMed
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Epidemiology of insulin-dependent diabetes mellitus around the Baltic Sea. The DIABALT Study Group.

https://arctichealth.org/en/permalink/ahliterature34729
Source
Horm Metab Res. 1996 Jul;28(7):340-3
Publication Type
Article
Date
Jul-1996
Author
J. Tuomilehto
M. Karvonen
Z. Padaiga
E. Tuomilehto-Wolf
K. Kohtamäki
Author Affiliation
Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland.
Source
Horm Metab Res. 1996 Jul;28(7):340-3
Date
Jul-1996
Language
English
Publication Type
Article
Keywords
Adolescent
Baltic States - ethnology
Child
Child, Preschool
Diabetes Mellitus, Type 1 - epidemiology - etiology
Female
Humans
Incidence
Infant
Infant, Newborn
Male
Regression Analysis
Risk factors
Seasons
Abstract
Great spatial variation in the incidence of IDDM is found among countries around the Baltic Sea, a relative small area on the global scale. We present recent data on IDDM incidence from countries around the Baltic Sea, monthly variation and time trends in incidence from the early 1980s to the early 1990s. The change in IDDM incidence was calculated from logarithms of incidence using linear regression. The incidence was high in the countries to the north and west from the Baltic Sea, being the highest in Finland (35 per 100,000/year) followed by Sweden (26), Denmark (22) and Norway (21). In the countries on the eastern and southern coast of the Baltic Sea the incidence was markedly lower, in Estonia the incidence (10) was the highest within these countries, though slightly less than one third of that in Finland, while it was in Lithuania 7, Latvia 7 and Poland 6. There was an increasing trend in incidence of IDDM in Finland, Norway and Poland. In Sweden the incidence increased from 1978 to 1984, but since then the trend has been flat. In Estonia, Latvia and Lithuania, no significant change in incidence was seen. The reasons for large differences observed in the incidence of IDDM between countries around the Baltic Sea area are unknown, but a complex interaction between genetic and environmental risk factors that can vary in different ethnic, socio-economic and cultural settings play an important role in this variation.
PubMed ID
8858381 View in PubMed
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Estimation of transmission probabilities in families ascertained through a proband with variable age-at-onset disease: application to the HLA A, B and DR loci in Finnish families with type 1 diabetes. The DiMe Study Group.

https://arctichealth.org/en/permalink/ahliterature198020
Source
Hum Hered. 2000 Sep-Oct;50(5):308-17
Publication Type
Article
Author
J. Pitkäniemi
P. Onkamo
E. Arjas
E. Tuomilehto-Wolf
J. Tuomilehto
Author Affiliation
Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland. Janne.Pitkaniemi@ktl.fi
Source
Hum Hered. 2000 Sep-Oct;50(5):308-17
Language
English
Publication Type
Article
Keywords
Adolescent
Age of Onset
Alleles
Child
Diabetes Mellitus, Type 1 - genetics - immunology
Finland
HLA-A Antigens - genetics
HLA-B Antigens - genetics
HLA-DR Antigens - genetics
Humans
Probability
Abstract
An open problem of some interest in the study of HLA has been the possible existence of transmission distortion in the human HLA complex. In this paper, transmission probabilities are estimated and tested using data on HLA A, B and DR loci genotypes of parents and offspring ascertained from the entire population of Finland (Childhood Diabetes in Finland Study) through one or more offspring diagnosed with insulin-dependent diabetes mellitus (IDDM) during the recruitment period from September 1986 to July 1989. First, we show how to get unbiased estimates of transmission probabilities from the family data collected in the disease registry of incident cases. This is accomplished by assuming that transmission of HLA genes to children in the general population is conditionally independent given the parents' genotypes, and the birth dates of all offspring. Based on the sampling (ascertainment) process in the study on Childhood Diabetes in Finland, younger siblings of the index child (the oldest proband) are independent of the ascertainment and therefore give rise to unbiased inference regarding allele transmission. The hypothesis of Mendelian transmission of alleles at each locus was tested using the standard chi(2) test. Goodness-of-fit of the Mendelian inheritance model to the individual locus data is calculated by maximizing the likelihood function over allele transmission intensities at each locus. The existence of a strong transmission distortion is not supported by this study at the loci considered.
PubMed ID
10878475 View in PubMed
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Evaluation of TAP1 polymorphisms with insulin dependent diabetes mellitus in Finnish diabetic patients. The Childhood Diabetes in Finland (DiMe) Study Group.

https://arctichealth.org/en/permalink/ahliterature208875
Source
Hum Immunol. 1997 Apr 1;53(2):159-66
Publication Type
Article
Date
Apr-1-1997
Author
L. Ma
A. Penfornis
X. Wang
D. Schoenfeld
E. Tuomilehto-Wolf
K. Metcalfe
G. Hitman
D. Faustman
Author Affiliation
Immunobiology Laboratory, Massachusetts General Hospital, Charlestown, USA.
Source
Hum Immunol. 1997 Apr 1;53(2):159-66
Date
Apr-1-1997
Language
English
Publication Type
Article
Keywords
ATP-Binding Cassette Transporters - genetics
Adolescent
Child
Child, Preschool
Diabetes Mellitus, Type 1 - epidemiology - genetics - immunology
Female
Finland - epidemiology
Genetic Markers - genetics
Genotype
HLA Antigens - genetics
Humans
Infant
Infant, Newborn
Male
Polymorphism, Genetic - immunology
Abstract
Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease with a strong association between disease and the HLA class II region. Because abnormal antigen processing, in part characterized by altered class I processing, has been identified in patients with IDDM, the TAP (transporter associated with antigen processing) genes located in the HLA class II region make attractive candidate genes for IDDM. Five coding region variants of TAP1 were typed in a cohort of well characterized Finnish patients with diabetes (n = 119) and compared to racially marched control subjects (n = 92). We found that although no single TAP1 polymorphism was associated with IDDM, a genotypic combination of Ile/Val at codon 333 with Asp/Asp at codon 637 was found more frequently in subjects with IDDM (9.4%) compared to controls (1.2%; p = 0.025). This could not be accounted for by an association with any particular haplotype defined by class I or class II serology.
PubMed ID
9129974 View in PubMed
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Evidence for importance of gender and birth cohort for risk of IDDM in offspring of IDDM parents.

https://arctichealth.org/en/permalink/ahliterature214652
Source
Diabetologia. 1995 Aug;38(8):975-82
Publication Type
Article
Date
Aug-1995
Author
J. Tuomilehto
T. Podar
E. Tuomilehto-Wolf
E. Virtala
Author Affiliation
Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland.
Source
Diabetologia. 1995 Aug;38(8):975-82
Date
Aug-1995
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age of Onset
Birth Order
Child
Cohort Studies
Diabetes Mellitus, Type 1 - epidemiology - genetics
Family Characteristics
Female
Finland - epidemiology
Humans
Incidence
Infant, Newborn
Male
Parents
Prevalence
Risk factors
Sex Characteristics
Sex Factors
Abstract
The risk of developing diabetes is higher in offspring of fathers than of mothers with insulin-dependent diabetes mellitus (IDDM). The reasons for this sex differential are unclear, as early studies were often selected and relatively small. We conducted a prospective study on the risk of IDDM in a cohort of 9,453 offspring from 5,255 Finnish parents with diabetes diagnosed before age 30 years. Age of first admission to the hospital was considered to be the age of diagnosis of IDDM in the offspring; IDDM occurred in 248 offspring. The risk of IDDM tended to be lower in the offspring of the same gender as the diabetic parent (adjusted risk ratio (RR) 0.78; p = 0.50). When offspring were of same gender as the diabetic parent, male offspring had a higher risk of IDDM than female offspring (RR 2.28; 95% confidence interval 1.53-3.38), whereas if the gender of the diabetic parent and the offspring were different, the risk in male offspring was lower (RR 0.43; 95% confidence interval 0.31-0.62). For the offspring of diabetic fathers, the cumulative risk by the age of 20 was higher (7.6%) than for those with diabetic mothers (3.5%) (p
PubMed ID
7589885 View in PubMed
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40 records – page 1 of 4.