Rapid HLA-DQB1 Genotyping for Four Alleles in the Assessment of Risk for IDDM in the Finnish Population

Ilonen, Jorma; Reijonen, Helena; Herva, Elja; Sjöroos, Minna; Iitiä, Antti; Lövgren, Timo; Veijola, Riitta; Knip, Mikael; Åkerblom, Hans K.

doi:10.2337/diacare.19.8.795

Cited by 124 publications

(109 citation statements)

References 27 publications

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“…Because this HLA-DQ2 molecule is also overrepresented in Type I diabetes, the frequent occurrence of coeliac disease in subjects with diabetes is believed to be connected with genetic predisposition [1]. In the Childhood Diabetes in Finland study, 43 % of children with diabetes and 24 % of population-based control subjects had the HLA-DQB1*02 allele [5]. Of the 427 non-diabetic siblings analysed in the present study, 29 % had HLA-DQB1*02.…”

Section: Discussionmentioning

confidence: 93%

“…The Childhood Diabetes in Finland study database was checked for cases of coeliac disease reported in questionnaires before the antibody screening. Genotyping of the HLA DQB1 locus was performed in 427 subjects by a PCR based hybridization assay using lanthanide labelled oligonucleotides and time-resolved fluorometry to detect the presence of Type I diabetes associated alleles [5].…”

Section: Methodsmentioning

confidence: 99%

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Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1 * 02 allele

et al. 2001

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Increased prevalence of coeliac disease in patients with Type I diabetes has been widely reported in Caucasian populations, with figures for prevalence varying from 1.0 to 7.8 % [1]. Certain HLA genotypes (especially, those positive for DR3-DQ2 haplotype) are more frequent in both of these diseases. First-degree relatives of patients with Type I diabetes have an increased risk for developing diabetes, a risk that is proportional to the degree of shared HLA risk alleles. It

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Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1 * 02 allele

et al. 2001

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“…HLA genotyping HLA was analysed on dried blood spots (DBS) on filters as described [28,29]. Filter samples (3 mm in diameter) of DBS were punched into 96-well PCR plates.…”

Section: Methodsmentioning

confidence: 99%

Diabetes-associated HLA genotypes affect birthweight in the general population

et al. 2005

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Aims/hypothesis: The aim of our study was to test the hypothesis that HLA genotypes conferring risk of diabetes, cord blood autoantibodies, or both are associated with increased birthweight. Methods: HLA genotypes were determined in dried blood spots of cord blood from a total of 16,709 children born to healthy mothers in the Diabetes Prediction in Skåne (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were determined in standard radioligand binding assays. Birthweight was adjusted for gestational age and divided into quartiles. The upper quartile was defined as high relative birthweight (HrBW) and the lower quartile as low relative birthweight (LrBW). Results: Genotypes conferring risk of type 1 diabetes were strongly associated with relative birthweight (rBW) (p=0.01). The high-risk HLA-DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (odds ratio [OR] [95% CI]=1.20 [1.08-1.33], p=0.0006). The HLA-DQB1*0603 allele, which is negatively associated with type 1 diabetes, was also associated with HrBW (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab were negatively associated with HrBW (OR [95% CI]= 0.72 [0.56-0.93], p=0.01). Regression analysis showed that the HLA-associated increase in rBW was independent of confounding factors. Conclusions/interpretation: HLA genotypes may be associated with intrauterine growth independent of type 1 diabetes risk. The epidemiological observation that high birthweight is a risk factor for type 1 diabetes could possibly result from a moderating effect on intrauterine growth of HLA genotypes conferring a high risk of diabetes.

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“…HLA The genotypes HLA-DQA1 and HLA-DQB1 were determined by PCR and sequence-specific probes as previously described [14,31,32]. HLA genotypes were available from 55 diabetic children, either from cord blood or from samples obtained at the diagnosis of diabetes.…”

Section: Control Childrenmentioning

confidence: 99%

Children developing type 1 diabetes before 6 years of age have increased linear growth independent of HLA genotypes

et al. 2008

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Aims/hypothesis High birthweight and increased childhood growth are risk factors for type 1 diabetes. Relative birthweight is associated with HLA genotypes that confer a high risk of diabetes. Our aims were to test whether young children prior to clinical onset of type 1 diabetes have increased: (1) birthweight or birth length standard deviation scores (SDS); (2) height development SDS; or (3) BMI SDS during first 18 months of life and whether these parameters are related to HLA genotypes or mid-parental height (MPH). Methods Birthweight, birth length, weight and height were obtained from 58 type 1 diabetes children and 155 controls matched for HLA or not in the Diabetes Prediction in Skåne study. Results Birth length SDS corrected for MPH was increased in children developing diabetes compared with all (p< 0.048) and with non-HLA-(p<0.050) but not with HLAmatched controls. Children developing diabetes had increased height gain at 0 to 18 months of age (p<0.005). Diabetic children were significantly taller from 6 to 18 months of age when correcting for MPH compared with non-HLA-matched as well as HLA-matched controls, but BMI was not increased. Conclusions/interpretation Birth length SDS was associated with diabetes risk HLA. When corrected for MPH, children developing diabetes were taller at birth than non-HLA-but not taller than HLA-matched controls. Diabetic children had increased MPH-corrected height up to 18 months of age compared with both HLA-and non-HLA-matched controls. High-risk HLA affects prenatal growth, but other factors may explain the increased postnatal linear growth in children developing diabetes.

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Rapid HLA-DQB1 Genotyping for Four Alleles in the Assessment of Risk for IDDM in the Finnish Population

Abstract: The near-automatic typing procedure developed is attractive for large-scale screening projects, such as diabetes prevention and intervention trials.

Cited by 124 publications

References 27 publications

Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1 * 02 allele

Prevalence of coeliac disease in siblings of patients with Type I diabetes is related to the prevalence of DQB1 * 02 allele

Diabetes-associated HLA genotypes affect birthweight in the general population

Children developing type 1 diabetes before 6 years of age have increased linear growth independent of HLA genotypes

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