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

• Published in: Diabetologia 2012-11, Vol.55 (11), p.2963-2969
• Main Authors: Söderlund, J., Forsblom, C., Ilonen, J., Thorn, L. M., Wadén, J., Parkkonen, M., Groop, P.-H.
• Format: Article
• Language: English
• Subjects: Adult; Arteriosclerosis; Atherosclerosis; Biological and medical sciences; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - genetics; Cardiovascular Diseases - mortality; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - mortality; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - genetics; Diabetic Nephropathies - mortality; Diabetic nephropathy; Drb1 protein; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Finland - epidemiology; Follow-Up Studies; Genetic testing; Genotype & phenotype; Genotypes; Haplotypes; Histocompatibility antigen HLA; Histocompatibility Antigens Class II - genetics; HLA-DQ beta-Chains - genetics; HLA-DRB1 Chains - genetics; Human Physiology; Humans; Inflammation; Internal Medicine; Kidney diseases; Leukocytes; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Morbidity; Mortality; Nephropathy; Prevalence; Regression analysis; Risk Factors; Smooth muscle
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-012-2670-6

Aims/hypothesis Patients with type 1 diabetes and kidney disease have a higher risk of cardiovascular events. HLA class II genes are expressed on infiltrated inflammatory cells and smooth-muscle cells in atherosclerotic plaques. We hypothesised that HLA class II haplotypes or genotypes might influence the risk of cardiovascular complications and death in Finnish type 1 diabetic patients. Methods We included 3,082 patients with type 1 diabetes from the Finnish Diabetic Nephropathy Study. We analysed the 12 and ten most common HLA II haplo- and genotypes, respectively, using χ 2 tests. The positive findings were analysed with three differently adjusted regression models with cardiovascular morbidity and death as endpoints. Different kidney status groups were analysed separately. Results At baseline, the common (DR1/10) - DQB1*05:01 haplotype (20.4%) and the (DR1/10) - DQB1*05:01 / DRB1*04:01 - DQB1*03:02 genotype (8.7%) were independently associated with cardiovascular disease in all kidney status groups, except in patients with normal AER. At follow-up (9.45 years; range 0.1–16.1 years), the (DR1/10) - DQB1*05:01 / DRB1*04:01 - DQB1*03:02 genotype was associated with cardiovascular mortality rates in patients with normal AER and microalbuminuria. Conclusions/interpretation 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.