SLC30A8 polymorphism and BMI complement HLA-A*24 as risk factors for poor graft function in islet allograft recipients

E.M. Balke, S. Demeester, D. Lee, P. Gillard, U. van de Velde, B.J. van der Auwera, Z. Ling, B.O. Roep, D.G. Pipeleers, B. Keymeulen, F.K. Gorus

Friday 16 march 2018

10:05 - 10:10h at Willem Burger Foyer

Categories: Clinical, Session (poster)

Parallel session: Poster session 6: Clinical

Aims/hypothesis

HLA-A*24 carriership hampers achievement of insulin independence in recipients of an islet allograft. However, less than half of those who failed 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

Retrospective analysis of a hospital-based patient cohort followed for 18 months post-transplantation. Forty C-peptide-negative type 1 diabetes patients received >2 million beta cells/kg body weight in one or two intraportal implantations under similar immunosuppression. Main outcome measurements included achievement and maintenance of acceptable graft function defined as <25% coefficient of variation of fasting glycaemia in presence of >1ng/mL (331pmol/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 also BMI≥ group median (23.9 kg/m²) 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 to achieve acceptable graft function (P=0.015). Maintenance of C-peptide positivity was mainly associated with older age at time of implantation. Only HLA-A*24 carriership independently predicted failure to maintain satisfactory graft function once achieved (P=0.017).

Conclusions/interpretation

HLA-A*24, the SLC30A8 T-allele, and high BMI associate with poor graft outcome. They should be considered in the interpretation of future transplantation trials.