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SLC30A8 polymorphism and BMI complement HLA-A24 as risk factors for poor graft function in islet allograft recipients
Ist Teil von
Diabetologia, 2018-07, Vol.61 (7), p.1623-1632
Ort / Verlag
Berlin/Heidelberg: Springer Berlin Heidelberg
Erscheinungsjahr
2018
Quelle
MEDLINE
Beschreibungen/Notizen
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% CV of 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
2
) 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
, the
SLC30A8
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