title: HLA class I and II alleles are associated with microvascular complications of type 1 diabetes.
abstract: Although HLA alleles are associated with type 1 diabetes, association with microvascular complications remains controversial. We tested HLA association with complications in multiplex type 1 diabetes families. Probands from 425 type 1 diabetes families from the Human Biological Data Interchange (HBDI) collection were analyzed. The frequencies of specific HLA alleles in patients with complications were compared with the frequencies in complications-free patients. The complications we examined were: retinopathy, neuropathy, and nephropathy. We used logistic regression models with covariates to estimate odds ratios. We found that the DRB1*03:01 allele is a protective factor for complications (OR=0.58; p=0.03), as is the DQA1*05:01-DQB1*02:01 haplotype found in linkage disequilibrium with DRB1*03:01 (OR=0.59; p=0.031). The DRB1*04:01 allele showed no evidence of association (OR=1.13; p=0.624), although DRB1*04:01 showed suggestive evidence when the carriers of the protective DRB1*03:01 were removed from the analysis. The class II DQA1*03:01-DQB1*03:02 haplotype was not associated with complications, but the class I allele B*39:06 (OR=3.27; p=0.008) suggested a strong positive association with complications. Our results show that in type 1 diabetes patients, specific HLA alleles may be involved in susceptibility to, or protection from, microvascular complications.
authors: Department of Epidemiology, Columbia University, Mailman School of Public Health, New York, NY, USA.
authors: E M
authors: EM
authors: Lipner
authors: Y
authors: Y
authors: Tomer
authors: J A
authors: JA
authors: Noble
authors: M C
authors: MC
authors: Monti
authors: J T
authors: JT
authors: Lonsdale
authors: B
authors: B
authors: Corso
authors: W C L
authors: WC
authors: Stewart
authors: D A
authors: DA
authors: Greenberg
mesh_terms: D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000145:classification / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D059811:HLA-DRB1 Chains
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