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

R. Rani, Ajay Sood, R. Goswami

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Type 1 diabetes (T1D) mellitus is a multifactorial autoimmune disease where more than 90% of insulin-producing pancreatic β 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-DRB1*0301 was significantly increased in the T1D patients along with associated DQB1*0201 followed by DRB1*0401 and DRB1*0405. DRB1*0701 was observed to be the most protective allele followed by DRB1*0403 and DRB1*0404. Although DQB1*0302 which is associated with both the protective and susceptible DR4 alleles was not significantly increased, heterozygous DQB1*0201, *0302 was significantly increased in the TID patients. Because INS-VNTR class I homozygosity was also significantly increased in the patients, simultaneous presence of DRB1*0301 along with homozygous INS-VNTR class I, gave a relative risk (RR) of 70.81. However, a similar analysis of DQB1*0201 and *0302 along with INS-VNTR alleles did not give such high RRs. Thus, the two independently assorting alleles at two loci i.e., DRB1*0301 and INS-VNTR class I, on two different chromosomes may have the potential to predict a prediabetic in North India.

Original languageEnglish (US)
Pages (from-to)145-155
Number of pages11
JournalTissue Antigens
Volume64
Issue number2
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

Fingerprint

Type 1 Diabetes Mellitus
Insulin
Alleles
Chromosomes
HLA Antigens
Major Histocompatibility Complex
Polymerase Chain Reaction
Minisatellite Repeats
Oligonucleotide Probes
Nucleic Acid Regulatory Sequences
Antigen Presentation
Restriction Fragment Length Polymorphisms
Thymus Gland
Autoimmune Diseases
India
Genes

Keywords

  • Human leukocyte antigen (HLA)
  • Insulin-linked variable number of tandem repeats (INS-VNTR)
  • Major histocompatibility complex
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Molecular basis of predisposition to develop type 1 diabetes mellitus in North Indians. / Rani, R.; Sood, Ajay; Goswami, R.

In: Tissue Antigens, Vol. 64, No. 2, 01.08.2004, p. 145-155.

Research output: Contribution to journalArticle

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