Type 1 diabetes mellitus (T1DM) (OMIM-222100), results from a cellular-mediated autoimmune destruction of the Beta-cell of the pancreas . T1DM is a disease of major public health concern [2–4]. The previous studies showed that in India, the prevalence of T1DM varies from about 1.6 to 10.5/100000/year [5, 6]. The epidemiological study conducted in South Indian population for four years, suggested the prevalence of T1DM in India is increasing. The overall prevalence of T1DM in Karnal district, a North Indian city with a population of 222017, is 10.20/100,000 population .
The genetic risk factors of T1DM are better understood than the environmental risk factors. Studies on Human and animal models show the MHC class II–mediated effects on the disease susceptibility . Early studies identified in the Human Leukocyte Antigen (HLA) genes, located on chromosome 6p21.31 as T1DM susceptibility genes. Resulting studies showed an association between the insulin gene on chromosome 11p15.5. The risk of T1DM is linked with about 18 regions of the genome. These regions, each of which may contain multiple genes, labeled IDDM1 to IDDM18. The best studied is IDDM1, which contains the HLA genes encode proteins of the immune response [9, 10].
HLA is one of the most polymorphic genetic systems in Human genome. IMGT/HLA database have reported 6,275 HLA alleles . Because the HLA class II molecules are polymorphic, they can embrace a wide variety of antigens in their antigen-binding groove and present them to diverse T-lymphocyte antigen receptors, triggering antigen recognition. Several studies have displayed HLA class II alleles, DQ and DR influence T1DM susceptibility. The contribution of the DQ molecules to overall disease susceptibility might be genotype dependent and/or may be influenced by the DRB1*04 allele on the haplotype .
The HLA-DQ heterodimers encoded by the DQA1*0301, DQB1*0302 and DQA1*0501, DQB1*0201 alleles have the strongest association with T1DM . These alleles are in LD with the HLA-DR4 and -DR3 alleles. In T1DM at least one allele of DR3 or DR4 is found in 95% in Europeans, and individuals with both DR3 and DR4 are particularly susceptible to T1DM, whereas, the DR2 allele is protective [14–16].
In North Indian T1DM patients also, the homozygosity and heterozygosity of DRB1*0301 and DRB1*04 alleles is significantly associated [17–19]. The Indian samples show HLA-C*0702 allele and shared HLA-B*0801 and DQB1*02 with the European 8.1AH [20–23].
The role of DP molecules has yet to be resolved satisfactorily. The results favor DPB1*0301 and DPB1*0202 alleles as predisposing for T1DM . Analysis of family-based data from the Human Biological Data Interchange (HBDI) repository and Italian studies, suggests the presence of a T1DM protective locus at or near DPB1*0101 . It is hypothesized that the strongest candidates for increasing T1DM risk among DR3-DQB1*0201/DR4-DQB1*0302 individuals is of alleles of DP and DRB1*04 subtypes and, in particular, the absence of reportedly protective alleles DPB1*0402 and/or DRB1*0403 .
There are some studies on HLA-DP in different ethnic groups mainly about HLA-DPB1. In a study from Sudan, there were no significant differences between Sudanese patient and control groups in HLA-DPB1 frequencies . Although, there was also no noticeable association between T1DM and HLA-DPB1 allele in Japanese . From Indian T1DM patients, so far no studies have been reported on DP molecules.
Although different methods exist to characterize the polymorphisms in HLA genes, the 12th International Histocompatibility Workshop suggested the Sequence Based Typing (SBT) methods . Therefore, we conducted a hospital-based case–control study in the West Bengal region of India to find out the role of HLA- DRB1, DQ and DP gene polymorphisms in progress T1DM.