SLC30A8 polymorphism and BMI complement HLA-A*24 as risk factors
for poor graft function in islet allograft recipients
Else M. Balke
Ursule Van de Velde
Bart J. Van der Auwera
Bart O. Roep
Daniël G. Pipeleers
Frans K. Gorus
Received: 5 January 2018 /Accepted: 12 March 2018 / Published online: 20 April 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Aims/hypothesis HLA-A*24 carriership hampers achievement of insulin independence in islet allograft recipients. However, less
than half of those who fail to achieve insulin independence carry the allele. We investigated whether genetic polymorphism at the
recipients’ zinc transporter 8-encoding SLC30A8 gene (rs13266634) could complement their HLA-A*24 status in predicting
functional graft outcome.
Methods We retrospectively analysed data of a hospital-based patient cohort followed for 18 months post transplantation. Forty
C-peptide-negative type 1 diabetic individuals who received >2 million beta cells (>4000 islet equivalents) per kg body weight in
one or two intraportal implantations under similar immunosuppression were genotyped for SLC30A8. Outcome measurements
included achievement and maintenance of graft function. Metabolic benefit was defined as <25% CVof fasting glycaemia in the
presence of >331 pmol/l C-peptide, in addition to achievement of insulin independence and maintenance of C-peptide positivity.
Results In multivariate analysis, HLA-A*24 positivity, presence of SLC30A8 CT or TT genotypes and BMI more than or equal to
the group median (23.9 kg/m
) were independently associated with failure to achieve insulin independence (p =0.015–0.046).
The risk increased with the number of factors present (p < 0.001). High BMI interacted with SLC30A8 T allele carriership to
independently predict difficulty in achieving graft function with metabolic benefit (p = 0.015). Maintenance of C-peptide
positivity was mainly associated with older age at the time of implantation. Only HLA-A*24 carriership independently predicted
failure to maintain acceptable graft function once achieved (p =0.012).
Conclusions/interpretation HLA-A*24,theSLC30A8 T allele and high BMI are associated with poor graft outcome and should
be considered in the interpretation of future transplantation trials.
Trial registration ClinicalTrials.gov NCT00798785 and NCT00623610
Keywords Body mass index
Genetics of type 1 diabetes
HLA class I
Human islet transplantation
Zinc transporter 8
Else M. Balke and Simke Demeester contributed equally as first authors.
Frans K. Gorus and Bart Keymeulen contributed equally as senior
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00125-018-4609-z) contains peer-reviewed but
unedited supplementary material, which is available to authorised users.
* Else M. Balke
Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan
103, 1090 Brussels, Belgium
Department of Endocrinology, University Hospitals Leuven,
Department of Immunohaematology and Blood Transfusion, Leiden
University Medical Center, Leiden, the Netherlands
Present address: Department of Diabetes Immunology, Diabetes and
Metabolism Research Institute, Beckman Research Institute at the
City of Hope, Duarte, CA, USA
Diabetologia (2018) 61:1623–1632