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The Influence of Rare Genetic Variation in SLC30A8 on Diabetes Incidence and beta-Cell Function

Author:
  • Liana K. Billings
  • Kathleen A. Jablonski
  • Rachel J. Ackerman
  • Andrew Taylor
  • Rebecca R. Fanelli
  • Jarred B. McAteer
  • Candace Guiducci
  • Linda M. Delahanty
  • Dana Dabelea
  • Steven E. Kahn
  • Paul Franks
  • Robert L. Hanson
  • Nisa M. Maruthur
  • Alan R. Shuldiner
  • Elizabeth J. Mayer-Davis
  • William C. Knowler
  • Jose C. Florez
Publishing year: 2014
Language: English
Pages: 926-930
Publication/Series: Journal of Clinical Endocrinology and Metabolism
Volume: 99
Issue: 5
Document type: Journal article
Publisher: The Endocrine Society

Abstract english

Context/Objective: The variant rs13266634 in SLC30A8, encoding a beta-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair beta-cell function, and test whether zinc intake modifies this risk. Design/Outcome: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate. Results: We detected a near-nominal association between a rare-variant genotype risk score and diabetes risk. Five common variants were associated with the oral disposition index. Various methods aggregating rare variants demonstrated associations with changes in oral disposition index and insulinogenic index during year 1 of follow-up. We did not find a clear interaction of zinc intake with genotype on diabetes incidence. Conclusions: Individual common and an aggregate of rare genetic variation in SLC30A8 are associated with measures of beta-cell function in the DPP. Exploring rare variation may complement ongoing efforts to uncover the genetic influences that underlie complex diseases.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Genetic and Molecular Epidemiology
  • ISSN: 1945-7197
Paul Franks
E-mail: paul [dot] franks [at] med [dot] lu [dot] se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49

60-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00