Noncoding Variations in the Gene Encoding Ceramide Synthase 6 are Associated with Type 2 Diabetes in a Large Indigenous Australian Pedigree

Twin Res Hum Genet. 2019 Apr;22(2):79-87. doi: 10.1017/thg.2019.13. Epub 2019 Apr 23.

Abstract

Type 2 diabetes (T2D) is a chronic disease that disproportionately affects Indigenous Australians. We have previously reported the localization of a novel T2D locus by linkage analysis to chromosome 2q24 in a large admixed Indigenous Australian pedigree (Busfield et al. (2002). American Journal of Human Genetics, 70, 349-357). Here we describe fine mapping of this region in this pedigree, with the identification of SNPs showing strong association with T2D: rs3845724 (diabetes p = 7 × 10-4), rs4668106 (diabetes p = 9 × 10-4) and rs529002 (plasma glucose p = 3 × 10-4). These associations were successfully replicated in an independent collection of Indigenous Australian T2D cases and controls. These SNPs all lie within the gene encoding ceramide synthase 6 (CERS6) and thus may regulate ceramide synthesis.

Keywords: chronic disease; diabetes; genetic association; indigenous health.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Australia / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics
  • Sphingosine N-Acyltransferase / genetics*

Substances

  • Membrane Proteins
  • CERS6 protein, human
  • Sphingosine N-Acyltransferase