Genetics of Type 1A Diabetes

Redondo, María J.

doi:10.1210/rp.56.1.69

Cited by 158 publications

(108 citation statements)

References 61 publications

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“…1,2 Useful clinical markers for genetic susceptibility to a disease are either familial aggregation or a variation in disease frequency, which are not explained by environmental, biochemical, or biological risk factors. Diabetic retinopathy (DR) displays these characteristics as clinical studies on human subjects with diabetes reveal substantial variation in the onset and severity of retinopathy that are not fully explained by the known risk factors such as duration of diabetes, level of glycaemic control, or concomitant vascular disease.…”

Section: Genetic Susceptibility To Diabetic Retinopathymentioning

confidence: 99%

Molecular genetics of microvascular disease in diabetic retinopathy

Warpeha

Chakravarthy

2003

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Section: Genetic Susceptibility To Diabetic Retinopathymentioning

confidence: 99%

Molecular genetics of microvascular disease in diabetic retinopathy

Warpeha

Chakravarthy

2003

Eye

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“…The cause of this increasing incidence is still unknown, as is the cause of the disease itself. Genetic factors, mainly HLA DR-DQ genotypes, are strong susceptibility factors [6]. However, among newly diagnosed type 1 diabetes patients only 10 to 15% have a first-degree relative with the disease [7] and the concordance rate between monozygotic twins is low [8,9], underlining the importance of environmental factors.…”

Section: Introductionmentioning

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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“…The incidence of type 1 diabetes before 15 years of age is increasing [1,2], especially for children diagnosed at an early age [3][4][5][6][7]. HLA susceptibility genes are strongly associated with type 1 diabetes [8][9][10][11]. Still the concordance rate for identical twins to develop disease is below 50% [12,13], which indicates that environmental factors are of importance.…”

Section: Introductionmentioning

confidence: 99%

“…HLA-DQB1*0302-A1*0301 (DQ8) and HLA-DQB1*0201-A1*0501 (DQ2) confer the highest risk for type 1 diabetes, especially when both are present in the genotype. Almost 90% of people with type 1 diabetes have at least one of these haplotypes [9].…”

Section: Introductionmentioning

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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Genetics of Type 1A Diabetes

Cited by 158 publications

References 61 publications

Molecular genetics of microvascular disease in diabetic retinopathy

Molecular genetics of microvascular disease in diabetic retinopathy

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

Diabetes-associated HLA genotypes affect birthweight in the general population

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