Elevated erythrocyte sodium-lithium countertransport activity occurs in diabetes and may be genetically mediated. The relation of this abnormality to the disease and its complications is unclear. To remove confounding genetic factors and the impact of complications, we studied sodium-lithium countertransport activity together with its kinetic components, maximal rate of turnover ...

Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are heterogeneous with respect to age and patient human leukocyte antigen (HLA) phenotype. We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets ...

HLA class II polymorphism in Moroccan IDDM patients has not been investigated so far. In this study, HLA-DRB1, -DQA1, and -DQB1 allele and haplotype frequencies were analyzed in 125 unrelated Moroccan IDDM patients and 93 unrelated healthy controls, all originating from the Souss region and mostly of Berber origin. Some ...

OBJECTIVE: To develop a resource, consisting of comprehensive data and lymphoblastoid cell lines, of well-characterized NIDDM families that will be available to the scientific community for genetic studies of NIDDM. RESEARCH DESIGN AND METHODS: Non-Hispanic white, Hispanic, African-American, and Japanese-American multiplex NIDDM families, with a minimum of one affected sib-pair, ...

Tumour necrosis factor (TNF) may be relevant to the pathogenesis of both pre-eclampsia and type 1 diabetes, and there is evidence than human TNF alpha responses to stimuli are HLA-DR dependent. To test the hypothesis that pre-eclampsia and diabetes may share a common immunogenetic susceptibility, 92 pre-eclampsia patients were compared ...

Insulin-dependent diabetes mellitus (IDDM) is a multigenic autoimmune disease. An IDDM susceptibility gene was mapped to chromosome 2q34. This gene may act early in diabetogenesis, because "preclinical" individuals also showed linkage. Human leukocyte antigen (HLA)-disparate, but not HLA-identical, sibs showed linkage, which was even stronger in families with affected females. ...

Four related male infants presented with neonatal diabetes mellitus, immune dysregulation with extremely high concentrations of immunoglobulin E, and intractable diarrhoea. They were all from one family, and all of them died. As far as is known this X-linked recessive disorder has not been described before. It is suggested that ...

Previous genome-wide mapping studies have provided suggestive linkage evidence for several novel susceptibility loci responsible for insulin-dependent diabetes mellitus (IDDM); however, the evidence was not sufficient to confirm the existence of these genes. We analyzed 265 Caucasian families with IDDM and report the first evidence that meets the standard for ...

To locate genes predisposing to insulin-dependent diabetes mellitus (IDDM), an autoimmune disorder resulting from destruction of the insulin-producing pancreatic cells, we are testing linkage of IDDM susceptibility to polymorphic markers across the genome using families with two or more IDDM children. A new susceptibility locus (IDDM11) has been localized to ...

To evaluate the association of autoimmunity to glutamic acid decarboxylase (GAD) with insulin-dependent diabetes mellitus (IDDM) and IDDM-associated human leukocyte antigen (HLA) types, we studied a unique group of 47 patients with autoimmune polyendocrine syndrome type 1, a recessive disease not associated with HLA. GAD65 antibodies (GAD65-Ab), GAD67-Ab, islet cell ...

Insulin-dependent diabetes mellitus (IDD) affects between one in 250 and one in 500 Americans. The inheritance of IDD is non-Mendelian and polygenic. Genetic susceptibility predominantly results from specific alleles in the HLA complex and insulin gene region. Autoimmune destruction of pancreatic beta cells leads to profound insulinopenia (Atkinson and Maclaren, ...

Transracial analysis is one method for distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA II alleles from those related to linkage disequilibrium. Black people have different DR-DQ relationships from other races and are a useful group to investigate HLA-D regions associated with IDDM. In this study, we compared ...

Insulin-dependent diabetes mellitus (IDDM) is linked to HLA factors on human chromosome 6 and strongly associated with the presence of autoantibodies against the glutamic acid decarboxylase isoform GAD65. These autoantibodies, GAD65Ab are detected both before and at the time of clinical diagnosis. Molecular sequencing of HLA alleles and PCR-based genotyping ...

MHC associations with IDDM in the Korean population were studied to investigate genetic susceptibility to this disorder. The frequencies of HLA-DR3, -DR4 and -DR9 were significantly higher in diabetic patients. However, the frequency of DR2 was significantly decreased in diabetic patients. DQA1*0301 and DQA1*0501 were positively and DQA1*0102 and DQA1*0201 ...

Whereas it is well known that the insulin gene (INS) region at 11p15.5 (IDDM2) confers susceptibility to insulin-dependent diabetes mellitus (IDDM), it is still controversial whether the parental origin of IDDM2 influences IDDM susceptibility. We have analysed the Pst I + 1127 polymorphism in 123 USA multiplex families and detected ...

Type 1 diabetes may appear at any age. The onset may be insidious and even asymptomatic for a long time. The prediabetic stage is characterized by genetic susceptibility, the presence of autoantibodies in serum, and gradual impairment of the beta-cell function. HLA-DQ-encoded heterodimers are strongly associated with increased risk/protection. Additional ...

The HLA haplotype B18-DR3 has a widespread geographical distribution, but has its greatest frequencies in Southern Europe, probably vestigial of the earliest populations of this region, particularly in the Pays Basque and Sardinia. This haplotype is of medical significance, being that most implicated as a factor of risk in insulin-dependent ...

OBJECTIVE: It has proved difficult to separate the role of the diabetic state as distinct from its complications in causing the elevation in erythrocyte sodium-lithium (Na-Li) countertransport activity that has been observed in diabetes. The present study sought to isolate the impact of diabetes on the countertransporter by studying groups ...

A negative association between insulin-dependent diabetes mellitus (IDDM) and HLA-DR, DQA1 or DQB1 was found in a large population-based investigation of childhood-onset patients (more than 420 patients) and controls (more than 340 controls) from Sweden. The relative risk was decreased for several haplotypes that were negatively associated with IDDM: DR15-DQA1*0102-DQB1*0602, ...

OBJECTIVE: To study the genetic contribution to the aetiology of insulin dependent diabetes mellitus. DESIGN: Historical cohort study of twins, with information on diabetes being gathered by questionnaire, verification of the diagnosis by the subject's diabetologist or general practitioner, and clinical examination in available twins. SETTING: Danish twin register and ...

Insulin-dependent diabetes mellitus (IDDM) is associated with susceptibility HLA class II alleles. Islet cell antibodies (ICA), detected by indirect immunofluorescence on pancreas sections, represent the best marker of the disease. Autoantibodies to glutamic acid decarboxylase (GADA), one major islet antigen, do not totally account for ICA reactivity, suggesting heterogeneity of ...

Genetic markers may be used to improve the prediction of insulin-dependent diabetes mellitus (type 1) in individuals with islet autoantibodies. In order to develop a risk assessment strategy for the Lombardy region of northern Italy based on genetic and immunological markers, we analyzed HLA DQA1 and DQB1 alleles in 60 ...

An association between insulin-dependent diabetes mellitus (IDDM) and polymorphisms of the insulin gene on chromosome 11p15 (INS) is a consistent finding in Europid populations. While one study suggested that the INS association is restricted to HLA-DR4-positive individuals, studies in other Europid populations have shown the disease-associated INS genotype to confer ...

The insulin autoimmune syndrome (IAS), or Hirata's disease, is characterized by the combination of fasting hypoglycemia, high concentration of total serum immunoreactive insulin, and presence of autoantibodies to native human insulin in serum. Autoantibody production is classified as monoclonal or polyclonal, with the majority of IAS cases classified as polyclonal. ...

Whether genetic susceptibility for insulin-dependent diabetes mellitus (IDDM) at the 5' insulin gene polymorphic region (5' INS) interacts with human leukocyte antigen (HLA)-DQ-linked disease risk and whether it is associated with autoantibody formation is presently controversial. Diabetes registries allow more systematic reassessment of these questions. Two hundred and ninety-six Caucasian ...

To investigate the relationship between human leukocyte antigen (HLA)-associated genetic factors and the development of beta-cell dysfunction, we performed sequential intravenous glucose tolerance tests (IVGTTs) on 81 islet cell antibody (ICA)-positive and/or insulin autoantibody-positive healthy siblings of children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). A lower glucose disappearance rate ...

The distribution of DRB1*04 alleles and DRB1/DQB1 haplotypes was analysed in 57 DR4+ caucasoid subjects with insulin-dependent diabetes mellitus (IDDM) and 96 DR4+ healthy controls selected on the basis of DR serology, and the findings were analysed in relation to age at diagnosis of IDDM. DNA samples were amplified using ...

Susceptibility to insulin-dependent disease is largely determined by alterations in an HLA gene. In addition to insulin, several other antigenic triggers have been identified. One of these, glutamic acid decarboxylase-65, appears to be a primary trigger and may be a key to future treatment. Experimentally, intrathymic or intravenous injection of ...

HLA-DQB1 alleles confer susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). We investigated whether the susceptibility alleles DQB1*0302 and DQB1*0201 affect progression to diabetes among islet cell antibody-positive (ICA+) first-degree relatives of IDDM patients and whether the protective allele DQB1*0602 can be found and is still protective among such relatives. ...

Insulin-dependent diabetes mellitus (IDDM) is characterized by autoimmune destruction of the insulin secreting beta-cells of the pancreas and subsequent disruption of glucose metabolism. The tendency of IDDM to cluster in families and the modest (36%) concordance rate in monozygotic twins indicates that both genetic and environmental factors contribute to IDDM ...

The polymorphism of the LST-1 gene (the human homologue of the mouse B144 gene) can be identified by Pvu II restriction enzyme digestion. We investigated the contribution of this RFLP to disease susceptibility in 117 patients with type I diabetes mellitus (IDDM), 110 with Graves' disease (GD) and 93 healthy ...

Among patients with insulin-dependent diabetes mellitus (IDDM), an excess of DR3 and DR4 alleles is classically described when compared with the general population. In addition, an excess of maternal DR3 and paternal DR4 alleles among patients (DR3DR4) is observed. In order to explain these observations, two alternative hypotheses can be ...

IDDM is known to be associated with genes of HLA complex, particularly alleles of HLA-DQ. The 40-kb TAP gene complex is located approximately 150 kb centrometric to the DQB1 locus. The TAP1-TAP2 protein heterodimer is required for normal expression levels of class I, molecules on the surface of cells. While ...

The (MHC) class II association with insulin-dependent diabetes mellitus (IDDM) is well documented. However, it is likely that genes within the MHC class III and the class I region also play a role in determining susceptibility to IDDM. In this study we have used a novel molecular probe to investigate ...

AIMS--To assess the relative diagnostic performance of the polymerase chain reaction (PCR) and non-isotopic in situ hybridisation (NISH) and to correlate these data with cytopathological assessment. METHODS--Paired analysis of human papillomavirus (HPV) detection was performed by PCR and NISH on exfoliated cervical cells from 122 women attending a routine gynaecological ...

Non-insulin-dependent diabetes mellitus has been recognized to be heterogeneous in etiology, with multiple subgroups. Several genes or chromosomal regions have been implicated in the development of the disease. In this study the association of HLA class II alleles and genotypes and the association of CD4 and CD3 polymorphisms were assessed ...

Epidemiological data are presented to support the hypothesis that the genetic contribution to disease pathogenesis in childhood onset diabetes is greatest in those presenting at a very early age. Analysis of family data from two national surveys of childhood onset Type 1 (insulin-dependent) diabetes (1988 in under 15s: 1992 in ...

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that results in the destruction of the pancreatic islet beta cells. Glutamic acid decarboxylase (GAD) has been recently indicated as a key autoantigen in the induction of IDDM in nonobese diabetic mice. In human diabetes, the mechanism by which the beta cells ...

To study the role of the HLA DQA1 gene and its interaction with DQB1 in the susceptibility of IDDM, subjects with insulin-dependent (type 1) diabetes mellitus and non-diabetic unrelated controls were recruited from a Chinese population living in northern Taiwan. HLA DQA1 exon 2 was enzymatically amplified by polymerase chain ...

Analysis of HLA-DQ molecules in a large study comprising 425 consecutively diagnosed Swedish Caucasians with IDDM and 367 age, sex and geographically matched controls confirms previous observations that: (a) DQB1*0302-DQA1*0301 confer susceptibility in a dominant manner, except when they are associated with DQB1*0602-DQA1*0102; (b) DQB1*0501-DQA1*0201 does not confer susceptibility to ...

We have performed intrafamilial and case-control association studies to examine the previously reported linkage disequilibrium between D2S152 and a type 1 diabetes susceptibility gene on chromosome 2q31-q33 (IDDM7). Significant linkage disequilibrium was observed in our subset of 47 Florida affected sibpair families (p < 0.02) but not in the other ...

Insulin-dependent diabetes mellitus (IDDM) is considered to be an autoimmune disease. Autoimmune diseases result from the breakdown of self-tolerance elicited by environmental factors on a susceptible genetic background. This reduced tolerance allows immunocompetent cells to attack normal structures present on an individual's tissues. The study of the T cells present ...

The follicular form of bronchiectasis originally described by Whitwell (1) has been associated with adenoviral infection. The present study compares resected lungs from 16 patients with follicular bronchiectasis (in 10 of whom a nonviral etiology was identified) with those from eight patients with a nonfollicular histologic pattern. DNA isolated from ...

The association between human leukocyte antigen (HLA) and insulin-dependent diabetes was studied in a large population-based investigation using genotyping of 425 new-onset patients, 0-14 years of age, and 367 matched control subjects. As many as 97% of patients compared with 75% of control subjects were positive for one or several ...

Although HLA class II genes are important in insulin-dependent diabetes (IDD), their influence on the expression of IDD-associated autoantibodies (aAb) is unclear. We compared HLA-DRB1 and DQB1 gene frequencies in several Caucasian groups: 191 normal controls, 378 IDD patients, and 357 non-diabetic relatives of which 250 had no aAb, 107 ...

Genetic susceptibility to type I diabetes is partly determined by genes located in the human leukocyte antigen (HLA) region on chromosome 6. It has been claimed that the transmission of HLA-encoded susceptibility is influenced by parental sex. Fathers are reported to transmit HLA-DR4 haplotypes more frequently to their diabetic offspring ...

The incidence of insulin-dependent diabetes in individuals with cystic fibrosis is nearly 100 times greater than in the general population. In the latter group, strong associations with specific HLA DQA1 and DQB1 alleles have been observed. To determine if a similar distribution of alleles occurs in cystic fibrosis patients with ...

TAP2 genes are placed within the HLA complex, have limited genetic variability and encode two main groups of peptide transporter proteins, the so-called TAP2*01 alleles, with a short ATP-binding domain, and the TAP2*0201 allele with a long domain. These transporters carry antigenic peptides from cytoplasm across the endoplasmic reticulum membrane ...

In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most common haplotype in insulin-dependent diabetic (IDDM) patients and has the highest haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes containing HLA-A alleles other than A2 are infrequent in the population and are not associated with ...

OBJECTIVE: To study the human leukocyte antigen (HLA)-DQB1 genetic background in the Chinese population in Taiwan and its association with the low incidence of insulin-dependent diabetes mellitus (IDDM) in this population. RESEARCH DESIGN AND METHODS: Forty-eight IDDM patients and 59 nondiabetic unrelated control subjects were recruited from the population in ...