Increased and decreased relative risk for noninsulin‐dependent diabetes mellitus conferred by HLA class II and by CD4 alleles

Abstract

Non‐insulin‐dependent diabetes mellitus has been recognized to be heterogeneous in etiology, with multiple subgroups. Several genes or chromosomal regions have been implicated in the development of the disease. In this study the association of HLA class II alleles and genotypes and the association of CD4 and CD3 polymorphisms were assessed in a large number of Belgian non‐insulin‐dependent diabetes mellitus patients. Furthermore, the importance of the DQα***Arg52/DQαlArg52 and the DQβlAsp57/DQβlAsp57 genotypes and the combination of both genotypes were examined. Our results show that in the HLA class II genes only the DQαlArg52+/DQαlArg52+ genotype was significantly associated with non‐insulin‐dependent diabetes mellitus compared with controls (p=0.011, RR=2.02). We also observed that the frequency of the CD4*A4/*A8 genotype and the CD4*A7 allele was significantly increased and decreased respectively in non‐insulin‐dependent diabetes mellitus patients as compared with the controls (p=0.018, RR=2.16 and p=0.0003, RR=0.49 respectively). These results therefore suggest that HLA class II and CD4 genes might independently contribute to the susceptibility for non‐insulin‐dependent diabetes mellitus and that these alleles and genotypes might identify subgroups of patients with different susceptibilities.

Lack of association between diabetic nephropathy and human leukocyte antigen type 2 (HLA II-DQ1) in patients with type 2 diabetes mellitus in west of Iran

“…In their study HLADQA1*0301, in diabetic nephropathy and the control group was 15.5% versus 8% (P < 0.01), HLA-DQA1*0501 was 16.6% versus 8.5% (P < 0.01), HLA-DQA1*0302 was 6.5% versus 13.5% (P < 0.01) and HLA-DQB1*0501 was 5.8% versus 14.5% (P < 0.01). Since there was no significant relationship between different alleles in the present study, which is not consistent with the study of Ma et al (16), it seems that the rate of HLA alleles and the association between them in the two groups of patients depends on racial and ethnic characteristics of (34). In Bahrain, relationship between type 2 diabetes with HLA-DQB1 and HLA-DRB1 was statistically significant (35).…”

Association of the HLA-DQA1 and HLA-DQB1 Alleles in Type 2 Diabetes Mellitus and Diabetic Nephropathy in the Han Ethnicity of China

“…Studies investigating the HLA-T2DM relationship are very limited, and the link between HLA and T2DM is still not conclusive. In two studies, using different genotyping methods, no association was found between T2DM and the HLA class II antigens (HLA-DR, HLA-DQ) in Punjabi Sikhs [19], while a positive association with HLA-DQA genes was reported for Belgians [20]. In Bahrainis, a population with a high prevalence of T2DM, T2DM was found significantly associated with both HLA-DRB1 and HLA-DQB1 genotypes, with some alleles appearing to confer susceptibility and others playing a protective role [11].…”