HLA class II is a factor in cardiovascular morbidity and mortality rates in patients with type 1 diabetes

Söderlund, Jenny; Forsblom, Carol; Ilonen, Jorma; Thorn, Lena M.; Wadén, Johan; Parkkonen, Maija; Groop, Per‐Henrik

doi:10.1007/s00125-012-2670-6

Cited by 11 publications

(14 citation statements)

References 24 publications

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“…Furthermore, HLA class II genes that are expressed on infiltrated inflammatory cells and smooth-muscle cells in atherosclerotic plaques are independently associated with cardiovascular events and death in a Finnish T1D study. [24]. …”

Section: Discussionmentioning

confidence: 99%

Early aggressive macrovascular disease and type 1 diabetes mellitus without chronic complications: a case report

Matheus

Gomes

2013

BMC Res Notes

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BackgroundType 1 diabetes (T1DM) is considered to be one of the most significant risk factors for the development of coronary artery disease (CAD). However, the specific risk predictor models for T1DM are subject to many limitations.Case presentationWe report the case of a 42-year-old Caucasian woman presenting with T1DM for 26 years. During her chronic hyperglycemic evolution (mean of HbA1c > 3 percentage points above the superior limit) without microvascular complications, this patient presented with early and aggressive coronary artery disease, despite the lack of classical risk factors for CADConclusionsThe rapidly progressive macrovascular disease observed in this case demonstrates the different degrees of aggressiveness and unpredictable clinical evolution observed in some cases. It also confirms the need for a multi-factorial, early and optimized clinical management regime.

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Section: Discussionmentioning

confidence: 99%

Early aggressive macrovascular disease and type 1 diabetes mellitus without chronic complications: a case report

Matheus

Gomes

2013

BMC Res Notes

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“…We successfully imputed the HLA haplotypes for 5152 out of 5162 individuals in our GWAS cohort with the SNP2HLA software [18] with default parameters and Type 1 Diabetes Genetic Consortium reference panel consisting of 3924 SNPs and 4‐digit HLA‐genotypes. We used previously genotyped HLA‐alleles (4‐ or 2‐digit accuracy) for 4279 FinnDiane study participants [19] for imputation quality validation. The imputed alleles for HLA‐DQA1, HLA‐DQB1 , and HLA‐DRB1 matched the genotyped alleles with ≥97.2% accuracy.…”

Section: Methodsmentioning

confidence: 99%

Genome‐wide search for genes affecting the age at diagnosis of type 1 diabetes

et al. 2020

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Background. Type 1 diabetes (T1D) is an autoimmune disease affecting individuals in the early years of life. Although previous studies have identified genetic loci influencing T1D diagnosis age, these studies did not investigate the genome with high resolution.Objective and methods. We performed a genome-wide meta-analysis for age at diagnosis with cohorts from Finland (Finnish Diabetic Nephropathy Study), the United Kingdom (UK Genetic Resource Investigating Diabetes) and Sardinia. Through SNP associations, transcriptome-wide association analysis linked T1D diagnosis age and gene expression.Results. We identified two chromosomal regions associated with T1D diagnosis age: multiple independent variants in the HLA region on chromosome 6 and a locus on chromosome 17q12. We performed gene-level association tests with transcriptome prediction models from two whole blood datasets, lymphocyte cell line, spleen, pancreas and small intestine tissues. Of the non-HLA genes, lower PNMT expression in whole blood, and higher IKZF3 and ZPBP2, and lower ORMDL3 and GSDMB transcription levels in multiple tissues were associated with lower T1D diagnosis age (FDR = 0.05). These genes lie on chr17q12 which is associated with T1D, other autoimmune diseases, and childhood asthma. Additionally, higher expression of PHF20L1, a gene not previously implicated in T1D, was associated with lower diagnosis age in lymphocytes, pancreas, and spleen. Altogether, the non-HLA associations were enriched in open chromatin in various blood cells, blood vessel tissues and foetal thymus tissue. Conclusion.Multiple genes on chr17q12 and PHF20L1 on chr8 were associated with T1D diagnosis age and only further studies may elucidate the role of these genes for immunity and T1D onset.

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“…We have previously genotyped the HLA alleles for the DQA1, DQB1 and DRB1 genes for 4,279 FinnDiane study participants (20). As almost half of the individuals in the pedigrees did not have HLA alleles typed, we imputed the HLA alleles using SNP2HLA software based on GWAS data from the HLA-region and the Type 1 Diabetes Genome Consortium's (T1DGC) reference genotype-HLA-allele panel (21).…”

Section: Hla Allele Prediction and Validation Of Hla Allele Imputationmentioning

confidence: 99%

Novel Linkage Peaks Discovered for Diabetic Nephropathy in Individuals With Type 1 Diabetes

et al. 2021

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HLA class II is a factor in cardiovascular morbidity and mortality rates in patients with type 1 diabetes

Abstract: The (DR1/10)-DQB105:01 haplotype and the (DR1/10)-DQB105:01/DRB104:01-DQB103:02 genotype are independently associated with cardiovascular events and death in Finnish type 1 diabetic patients.

Cited by 11 publications

References 24 publications

Early aggressive macrovascular disease and type 1 diabetes mellitus without chronic complications: a case report

Early aggressive macrovascular disease and type 1 diabetes mellitus without chronic complications: a case report

Genome‐wide search for genes affecting the age at diagnosis of type 1 diabetes

Novel Linkage Peaks Discovered for Diabetic Nephropathy in Individuals With Type 1 Diabetes

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HLA class II is a factor in cardiovascular morbidity and mortality rates in patients with type 1 diabetes

Abstract: The (DR1/10)-DQB1*05:01 haplotype and the (DR1/10)-DQB1*05:01/DRB1*04:01-DQB1*03:02 genotype are independently associated with cardiovascular events and death in Finnish type 1 diabetic patients.

Cited by 11 publications

References 24 publications

Early aggressive macrovascular disease and type 1 diabetes mellitus without chronic complications: a case report

Early aggressive macrovascular disease and type 1 diabetes mellitus without chronic complications: a case report

Genome‐wide search for genes affecting the age at diagnosis of type 1 diabetes

Novel Linkage Peaks Discovered for Diabetic Nephropathy in Individuals With Type 1 Diabetes

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Product

Resources

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Abstract: The (DR1/10)-DQB105:01 haplotype and the (DR1/10)-DQB105:01/DRB104:01-DQB103:02 genotype are independently associated with cardiovascular events and death in Finnish type 1 diabetic patients.