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

Diabetologia. 2012 Nov;55(11):2963-9. doi: 10.1007/s00125-012-2670-6. Epub 2012 Aug 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / mortality*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / mortality*
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / mortality
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • HLA-DQ beta-Chains / genetics*
  • HLA-DRB1 Chains / genetics*
  • Haplotypes
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Male
  • Middle Aged
  • Morbidity
  • Prevalence
  • Risk Factors

Substances

  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class II