Paternally transmitted IDDM2 influences diabetes susceptibility despite biallelic expression of the insulin gene in human pancreas

Marilyn M. Bui, De Fang Luo, Jan Y. She, Noel K. Maclaren, Andrew Muir, Glenys Thomson, She Jin-Xiong

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Whereas it is well known that the insulin gene (INS) region at 11p15.5 (IDDM2) confers susceptibility to insulin-dependent diabetes mellitus (IDDM), it is still controversial whether the parental origin of IDDM2 influences IDDM susceptibility. We have analysed the PstI+1127 polymorphism in 123 USA multiplex families and detected linkage only in male meioses using the affected sibpair analysis (P = 0.009). Application of the transmission/disequilibrium test (TDT) found significantly increased transmission of the IDDM-associated INS allele from fathers heterozygous for INS to their diabetic offspring (P = 0.00002), but the transmission from heterozygous mothers was not significantly different from expectation. In non-diabetic families, the transmission from heterozygous for INS was not significantly different from random expectation in either paternal or maternal meioses. Maternal imprinting of the INS gene in pancreatic islets was originally considered the most favorable explanation for the observed gender-related difference. However, our study has demonstrated biallelic expression of INS in pancreatic tissues from human fetuses and thus suggests that INS is probably not imprinted in the pancreatic islets.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalJournal of Autoimmunity
Volume9
Issue number1
DOIs
StatePublished - Feb 1996
Externally publishedYes

Keywords

  • Gene expression
  • Genomic imprinting
  • Insulin gene
  • Linkage analysis
  • Transmission bias

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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