Molecular basis of predisposition to develop type 1 diabetes mellitus in North Indians.

Type 1 diabetes (T1D) mellitus is a multifactorial autoimmune disease where more than 90% of insulin-producing pancreatic beta cells are destroyed before the clinical manifestations, warranting a need to identify the children predisposed to get the disease. Of the 20 genomic intervals implicated for the risk to develop T1D, the major histocompatibility complex (MHC) region on chromosome 6p21.31 (IDDM1) has been the major contributor, followed by 5' regulatory region of the insulin (INS) gene on chromosome 11p15.5 (IDDM2). MHC has a role in antigen presentation and IDDM2 has been shown to have a role in transcription of insulin in the thymus. Hence, alleles of human leukocyte antigen (HLA)-DRB1, DQB1, and insulin-linked variable number of tandem repeats (INS-VNTR) were studied in 110 T1D patients and 112 healthy controls using polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes (PCR-SSOP) and PCR restriction fragment length polymorphism (PCR-RFLP), respectively. HLA-DRB10301 was significantly increased in the T1D patients along with associated DQB10201 followed by DRB10401 and DRB10405. DRB10701 was observed to be the most protective allele followed by DRB10403 and DRB10404. Although DQB10302 which is associated with both the protective and susceptible DR4 alleles was not significantly increased, heterozygous DQB10201, 0302 was significantly increased in the TID patients. Because INS-VNTR class I homozygosity was also significantly increased in the patients, simultaneous presence of DRB10301 along with homozygous INS-VNTR class I, gave a relative risk (RR) of 70.81. However, a similar analysis of DQB10201 and 0302 along with INS-VNTR alleles did not give such high RRs. Thus, the two independently assorting alleles at two loci i.e., DRB10301 and INS-VNTR class I, on two different chromosomes may have the potential to predict a prediabetic in North India.