HLA class II is a factor in cardiovascular morbidity and mortality rates in patients with type 1 diabetes.
OBJECTIVE
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
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.
Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, 00014 Helsinki, Finland.
J
J
Söderlund
C
C
Forsblom
J
J
Ilonen
L M
LM
Thorn
J
J
Wadén
M
M
Parkkonen
P-H
PH
Groop
D000328:Adult; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000401:mortality; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D015995:Prevalence; D012307:Risk Factors
D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II